Stilbene derivative and method for preparing same

ABSTRACT

A stilbene derivative and a method of preparing the A stilbene derivative are disclosed. The stilbene derivative is provided for inhibiting the function of cyclophilin, which is effective at the prevention of cyclophilin-related diseases or at the treatment of symptoms of such diseases. The method of preparing a stilbene derivative includes reacting a phenylacetonitrile derivative with a benzaldehyde derivative.

INCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATIONS

Any and all applications for which a foreign or domestic priority claimis identified in the Application Data Sheet as filed with the presentapplication are hereby incorporated by reference under 37 CFR 1.57.

TECHNICAL FIELD

The present invention relates to a novel stilbene derivative forinhibiting the function of cyclophilin, which has an improvedpharmaceutical profile, and to a method of preparing the same.

BACKGROUND

Cyclophilin is known to be an effective drug target for many diseases,including viral infection diseases such as hepatitis B virus (HBV),hepatitis C virus (HCV), human immunodeficiency virus (HIV), influenzavirus, etc.; diseases caused by inflammatory responses, such ascardiovascular diseases; rheumatoid arthritis; sepsis; asthma;periodontitis; aging; alopecia; neurodegenerative diseases caused bymitochondrial dysfunction; cancer and the like (Nigro P, et al, CellDeath Dis 2013, 4, e888).

Cyclophilin (CyP), which is a protein belonging to the immunophilinfamily, is found in all cells of all organisms, both prokaryotes andeukaryotes, and has been structurally well preserved throughoutevolution. A human contains a total of 16 intrinsic proteins presenttherein, including seven main CyPs, namely CyP A, CyP B, CyP C, CyP D,CyP E, CyP 40, and CyP NK.

Cyclophilin is found in most cells in the human body, and CyP A and CyP40 in mammals have cytoplasmic signal sequences, whereas CyP B and CyP Chave N-terminal signal sequences that target to the endoplasmicreticulum. CyP D has a signal sequence that directs to mitochondria, CyPE has an amino-terminal RNA binding domain and is located in thenucleus, and CyP 40 has a TPR and is located in the cytoplasm. Human CyPNK is the largest CyP, with a large hydrophilic and positively chargedcarboxyl end, and is located in the cytoplasm.

Cyclophilin is a multifunctional protein involved in cellular processesand is responsible for essential functions in cells. Cyclophilin hasbeen proven to have enzymatic properties of catalyzing cis-transisomerization of peptidyl-prolyl bonds. Thus, cyclophilin is referred toas peptidyl prolyl cis-trans isomerase (PPIase), which may act as anacceleration factor in proper folding of newly synthesized proteins.PPIase is also involved in repairing damaged proteins due toenvironmental stresses, including thermal stress, ultraviolet radiation,changes in the pH of the cellular environment, and oxidant treatment.This function is known as molecular chaperone activity. The PPIaseactivity of cyclophilin has also been proven to be involved inintracellular protein trafficking, mitochondrial function and pre-mRNAprocessing.

Cyclosporine, one of available cyclophilin inhibitors, binds in thehydrophobic pocket of CyP A to thus inhibit PPIase activity. CyP A is aprototype of the cyclophilin family, and shows very high sequencehomology with CyP B, CyP C, and CyP D in humans. The binding pockets ofall cyclophilins are formed by approximately 109 amino acids,corresponding to highly conserved regions, and the sequence homologybetween CyP A and CyP D is 100%. Therefore, CyP A binding affinity isthe best predictor of CyP D binding affinity and vice versa.

Such sequence homology between cyclophilins suggests that not only CyP Dbut also all cyclophilins are potential targets for functionalinhibitors having binding affinity to CyP A, indicating that functionalinhibitors of CyP A may be useful for the treatment of many diseasescaused by numerous intracellular processes to which cyclophilins arerelated.

The disclosure of this section is to provide background of theinvention. Applicant notes that this section may contain informationavailable before this application. However, by providing this section,Applicant does not admit that any information contained in this sectionconstitutes prior art.

SUMMARY

Accordingly, the present invention is intended to provide a compound forinhibiting the function of cyclophilin, which has an improvedpharmaceutical profile so as to prevent diseases, including viralinfection diseases such as HBV, HCV, HIV, influenza and the like,cardiovascular diseases, rheumatoid arthritis, sepsis, asthma,periodontitis, aging, alopecia, neurodegenerative diseases, cancer, etc.or to treat symptoms of such diseases, and also to provide a method ofpreparing the same.

Therefore, the present invention provides a compound that is capable ofinhibiting the function of cyclophilin. The present invention provides astilbene derivative, represented by Chemical Formula 1 below, apharmaceutically acceptable salt, a hydrate, a hydrated salt, apolymorphic crystal structure, a racemate, a diastereoisomer, or anenantiomer thereof. It is used for the prevention of cyclophilin-relateddiseases or for the treatment of symptoms of such diseases.

In Chemical Formula 1,

A is CRa or N,

B is CRb or N,

G is CRe or N,

J is CRf or N,

M is CRg or N,

D, E, and L are CRh or N,

Rx is H, CH₃, CN, NH₂, F, Cl, Br or I,

wherein when Rx is H, CH₃, NH₂, F, Cl, Br or I,

Ra is hydrogen, NO₂, CN, OH, a C1-C5 alkyl group, a C2-C10 alkenylgroup, a C1-C2 alkoxy group, —COOR1 (R1 is hydrogen or a C1-C5 alkylgroup) or —OCOR2 (R2 is a C1-C5 alkyl group),

Rb is hydrogen, a C1-C20 alkyl group, a C2-C10 alkenyl group, a C1-C10alkoxy group, —COOR1 (R1 is hydrogen or a C1-C5 alkyl group) or —OCOR2(R2 is a C1-C5 alkyl group),

Rc is OH, NO₂, a C1-C20 alkyl group, a C3-C10 cycloalkyl group, a C2-C10alkoxy group, a C6-C12 aryl, a C5-C12 heterocyclic group, —NR3R4 (R3 ishydrogen, a C1-C20 alkyl group or a C6-C12 aryl, R4 is hydrogen, aC1-C20 alkyl group or a C6-C12 aryl, and R3 and R4 may be linked to forma heterocycle, further containing at least one hetero atom), —COOR5 (R5is a C1-C20 alkyl group, a C6-C12 aryl or a C3-C10 cycloalkyl group),—OCOR6 (R6 is a C1-C20 alkyl group, a C6-C12 aryl or a C3-C10 cycloalkylgroup), —NR7CYR8 (Y is O or S, R7 is hydrogen or a C1-C5 alkyl group,and R8 is a C1-C20 alkyl group, a C6-C12 aryl, a C3-C10 cycloalkyl groupor a C5-C12 heterocyclic group), —NHS(O)₂R9 (R9 is a C6-C12 aryl or aC5-C12 heterocyclic group), or —COR10 (R10 is a C1-C20 alkyl group, aC6-C12 aryl, a C3-C10 cycloalkyl group or a C5-C12 heterocyclic group),

Rd is halogen, NO₂, COOH, CN, a C2-C20 alkyl group, a C3-C10 cycloalkylgroup, a C1-C10 alkoxy group, a C6-C12 aryl, a C5-C12 heterocyclicgroup, —NR3R4 (R3 is hydrogen, a C1-C20 alkyl or a C6-C12 aryl, R4 ishydrogen, a C1-C20 alkyl or a C6-C12 aryl, and R3 and R4 may be linkedto form a heterocycle, further containing at least one hetero atom),—COOR5 (R5 is a C1-C20 alkyl group, a C6-C12 aryl or a C3-C10 cycloalkylgroup), —OCOR6 (R6 is a C1-C20 alkyl group, a C6-C12 aryl or a C3-C10cycloalkyl group), —NR7CYR8 (Y is O or S, R7 is hydrogen or a C1-C5alkyl group, and R8 is a C1-C20 alkyl group, a C6-C12 aryl, a C3-C10cycloalkyl group or a C5-C12 heterocyclic group), —NHS(O)₂R9 (R9 is aC6-C12 aryl or a C5-C12 heterocyclic group), or COR10 (R10 is a C1-C20alkyl group, a C6-C12 aryl, a C3-C10 cycloalkyl group or a C5-C12heterocyclic group),

Re is hydrogen, NH₂, OH, CN, a C1-C20 alkyl group, a C2-C10 alkenylgroup, a C1-C10 alkoxy, a C6-C12 aryl, a C5-C12 heterocyclic group,—NR7CYR8 (Y is O or S, R7 is hydrogen or a C1-C5 alkyl group, and R8 isa C1-C20 alkyl group, a C6-C12 aryl, a C3-C10 cycloalkyl group or aC5-C12 heterocyclic group) or —NHS(O)₂R9 (R9 is a C6-C12 aryl or aC5-C12 heterocyclic group),

Rf is hydrogen, NH₂, OH, NO₂, a C1-C4 alkyl group, a C2-C10 alkenylgroup, a C1-C4 alkoxy group, a C6-C12 aryl, a C5-C12 heterocyclic group,—NHR11 (R11 is a C1-C2 alkyl group), —COOR12 (R12 is a C1-C2 alkylgroup), —OCOR13 (R13 is a C1-C2 alkyl group), or —COR14 (R14 is a C1-C2alkyl group),

Rg is hydrogen, NH₂, OH, halogen, NO₂, COOH, CN, a C1-C20 alkyl group, aC2-C10 alkenyl group, a C3-C10 cycloalkyl group, a C1-C10 alkoxy group,a C6-C12 aryl, a C5-C12 heterocyclic group, —NR3R4 (R3 is hydrogen, aC1-C20 alkyl or a C6-C12 aryl, R4 is hydrogen, a C1-C20 alkyl or aC6-C12 aryl, and R3 and R4 may be linked to form a heterocycle, furthercontaining at least one hetero atom), —COOR5 (R5 is a C1-C20 alkylgroup, a C6-C12 aryl or a C3-C10 cycloalkyl group), —OCOR6 (R6 is aC1-C20 alkyl group, a C6-C12 aryl or a C3-C10 cycloalkyl group),—NR7CYR8 (Y is O or S, R7 is hydrogen or a C1-C5 alkyl group, and R8 isa C1-C20 alkyl group, a C6-C12 aryl, a C3-C10 cycloalkyl group or aC5-C12 heterocyclic group), —NHS(O)₂R9 (R9 is a C6-C12 aryl or a C5-C12heterocyclic group), or —COR10 (R10 is a C1-C20 alkyl group, a C6-C12aryl, a C3-C10 cycloalkyl group or a C5-C12 heterocyclic group), and

Rh is hydrogen, NH₂, OH, a C1-C5 alkyl group or a C2-C10 alkenyl group,

when Rx is CN,

Ra is hydrogen,

Rb is hydrogen, a C1-C20 alkyl group, a C2-C10 alkenyl group, a C1-C10alkoxy group, —COOR1 (R1 is hydrogen or a C1-C5 alkyl group) or —OCOR2(R2 is a C1-C5 alkyl group),

Rc is OH, NO₂, a C1-C20 alkyl group, a C3-C10 cycloalkyl group, a C2-C10alkoxy group, a C6-C12 aryl, a C5-C12 heterocyclic group, —NR3R4 (R3 ishydrogen, a C1-C20 alkyl group or a C6-C12 aryl, R4 is hydrogen, aC1-C20 alkyl group or a C6-C12 aryl, and R3 and R4 may be linked to forma heterocycle, further containing at least one hetero atom), —COOR5 (R5is a C1-C20 alkyl group, a C6-C12 aryl or a C3-C10 cycloalkyl group),—OCOR6 (R6 is a C1-C20 alkyl group, a C6-C12 aryl or a C3-C10 cycloalkylgroup), —NR7CYR8 (Y is O or S, R7 is hydrogen or a C1-C5 alkyl group,and R8 is a C1-C20 alkyl group, a C6-C12 aryl, a C3-C10 cycloalkyl groupor a C5-C12 heterocyclic group), —NHS(O)₂R9 (R9 is a C6-C12 aryl or aC5-C12 heterocyclic group), or —COR10 (R10 is a C1-C20 alkyl group, aC6-C12 aryl, a C3-C10 cycloalkyl group, or a C5-C12 heterocyclic group),

Rd is hydrogen, halogen, NO₂, COOH, CN, a C2-C20 alkyl group, a C3-C10cycloalkyl group, a C1-C10 alkoxy group, a C6-C12 aryl, a C5-C12heterocyclic group, —NR3R4 (R3 is hydrogen, a C1-C20 alkyl group or aC6-C12 aryl, R4 is hydrogen, a C1-C20 alkyl group or a C6-C12 aryl, andR3 and R4 may be linked to form a heterocycle, further containing atleast one hetero atom), —COOR5 (R5 is a C1-C20 alkyl group, a C6-C12aryl or a C3-C10 cycloalkyl group), —OCOR6 (R6 is a C1-C20 alkyl group,a C6-C12 aryl or a C3-C10 cycloalkyl group), —NR7CYR8 (Y is O or S, R7is hydrogen or a C1-C5 alkyl group, and R8 is a C1-C20 alkyl group, aC6-C12 aryl, a C3-C10 cycloalkyl group or a C5-C12 heterocyclic group),—NHS(O)₂R9 (R9 is a C6-C12 aryl or a C5-C12 heterocyclic group), orCOR10 (R10 is a C1-C20 alkyl group, a C6-C12 aryl, a C3-C10 cycloalkylgroup or a C5-C12 heterocyclic group),

Re is hydrogen, CN, a C2-C20 alkyl group, a C2-C10 alkenyl group, aC1-C10 alkoxy, a C6-C12 aryl, a C5-C12 heterocyclic group, —NR7CYR8 (Yis O or S, R7 is hydrogen or a C1-C5 alkyl group, and R8 is a C1-C20alkyl group, a C6-C12 aryl, a C3-C10 cycloalkyl group or a C5-C12heterocyclic group) or —NHS(O)₂R9 (R9 is a C6-C12 aryl or a C5-C12heterocyclic group),

Rf and Rg are each hydrogen, and

Rh is hydrogen, a C1-C5 alkyl group or a C2-C10 alkenyl group,

the hetero atom of the heterocyclic group may be at least one selectedfrom the group consisting of nitrogen, oxygen and sulfur,

the alkyl group may be substituted with at least one substituentselected from the group consisting of OH, amine, a C6-C12 aryl, a C5-C10heterocyclic group and a C3-C10 cycloalkyl group,

the alkoxy group may be substituted with at least one substituentselected from the group consisting of halogen, a C6-C12 aryl, a C3-C10cycloalkyl group, amine and an aminocarbonyl group,

the heterocyclic group may be substituted with at least one substituentselected from the group consisting of an alkyl group, anamine-substituted alkyl group, amine, an amide group and a carboxylgroup,

the aryl may be substituted with at least one substituent selected fromthe group consisting of halogen, an alkyl group, a hydroxyl group, analkoxy group, a carboxyl group, an ester group, a nitro group and anamine group,

A, B, D, E, G, J, L and M may be linked with an adjacent group to form afused ring, and

Rd cannot be NO₂ when Rb is CH₃.

According to the present invention, stilbene derivatives are effectiveat inhibiting the function of cyclophilin, and are thus useful for theprevention of cyclophilin-related diseases, including viral infectiondiseases, such as hepatitis C virus (HCV), hepatitis B virus (HBV),human immunodeficiency virus (HIV), avian influenza (AI) virus and thelike, cardiovascular diseases, rheumatoid arthritis, sepsis, asthma,periodontitis, aging, alopecia, neurodegenerative diseases, cancer,etc., or for the treatment of symptoms of such diseases. Moreover, thestilbene derivatives of the invention can be used in combination withexisting therapeutic agents to thus increase the therapeutic effects.

DESCRIPTION OF THE SPECIFIC EMBODIMENTS

Hereinafter, a detailed description will be given of the presentinvention.

The present invention addresses a stilbene derivative represented byChemical Formula 1 below. The stilbene derivative of the presentinvention has a structure appropriate for binding to an active pocketthat is maintained in any protein having the function of cyclophilin andis thus useful as a cyclophilin inhibitor.

In Chemical Formula 1,

A is CRa or N,

B is CRb or N,

G is CRe or N

J is CRf or N,

M is CRg or N,

D, E, and L are CRh or N,

Rx is H, CH₃, CN, NH₂, F, Cl, Br or I,

wherein when Rx is H, CH₃, NH₂, F, Cl, Br or I,

Ra is hydrogen, NO₂, CN, OH, a C1-C5 alkyl group, a C2-C10 alkenylgroup, a C1-C2 alkoxy group, —COOR1 (R1 is hydrogen or a C1-C5 alkylgroup) or —OCOR2 (R2 is a C1-C5 alkyl group),

Rb is hydrogen, a C1-C20 alkyl group, a C2-C10 alkenyl group, a C1-C10alkoxy group, —COOR1 (R1 is hydrogen or a C1-C5 alkyl group) or —OCOR2(R2 is a C1-C5 alkyl group),

Rc is OH, NO₂, a C1-C20 alkyl group, a C3-C10 cycloalkyl group, a C2-C10alkoxy group, a C6-C12 aryl, a C5-C12 heterocyclic group, —NR3R4 (R3 ishydrogen, a C1-C20 alkyl group or a C6-C12 aryl, R4 is hydrogen, aC1-C20 alkyl group or a C6-C12 aryl, and R3 and R4 may be linked to forma heterocycle, further containing at least one hetero atom), —COOR5 (R5is a C1-C20 alkyl group, a C6-C12 aryl or a C3-C10 cycloalkyl group),—OCOR6 (R6 is a C1-C20 alkyl group, a C6-C12 aryl or a C3-C10 cycloalkylgroup), —NR7CYR8 (Y is O or S, R7 is hydrogen or a C1-C5 alkyl group,and R8 is a C1-C20 alkyl group, a C6-C12 aryl, a C3-C10 cycloalkyl groupor a C5-C12 heterocyclic group), —NHS(O)₂R9 (R9 is a C6-C12 aryl or aC5-C12 heterocyclic group), or —COR10 (R10 is a C1-C20 alkyl group, aC6-C12 aryl, a C3-C10 cycloalkyl group or a C5-C12 heterocyclic group),

Rd is halogen, NO₂, COOH, CN, a C2-C20 alkyl group, a C3-C10 cycloalkylgroup, a C1-C10 alkoxy group, a C6-C12 aryl, a C5-C12 heterocyclicgroup, —NR3R4 (R3 is hydrogen, a C1-C20 alkyl or a C6-C12 aryl, R4 ishydrogen, a C1-C20 alkyl or a C6-C12 aryl, and R3 and R4 may be linkedto form a heterocycle, further containing at least one hetero atom),—COOR5 (R5 is a C1-C20 alkyl group, a C6-C12 aryl or a C3-C10 cycloalkylgroup), —OCOR6 (R6 is a C1-C20 alkyl group, a C6-C12 aryl or a C3-C10cycloalkyl group), —NR7CYR8 (Y is O or S, R7 is hydrogen or a C1-C5alkyl group, and R8 is a C1-C20 alkyl group, a C6-C12 aryl, a C3-C10cycloalkyl group or a C5-C12 heterocyclic group), —NHS(O)₂R9 (R9 is aC6-C12 aryl or a C5-C12 heterocyclic group), or COR10 (R10 is a C1-C20alkyl group, a C6-C12 aryl, a C3-C10 cycloalkyl group or a C5-C12heterocyclic group),

Re is hydrogen, NH₂, OH, CN, a C1-C20 alkyl group, a C2-C10 alkenylgroup, a C1-C10 alkoxy, a C6-C12 aryl, a C5-C12 heterocyclic group,—NR7CYR8 (Y is O or S, R7 is hydrogen or a C1-C5 alkyl group, and R8 isa C1-C20 alkyl group, a C6-C12 aryl, a C3-C10 cycloalkyl group or aC5-C12 heterocyclic group) or —NHS(O)₂R9 (R9 is a C6-C12 aryl or aC5-C12 heterocyclic group),

Rf is hydrogen, NH₂, OH, NO₂, a C1-C4 alkyl group, a C2-C10 alkenylgroup, a C1-C4 alkoxy group, a C6-C12 aryl, a C5-C12 heterocyclic group,—NHR11 (R11 is a C1-C2 alkyl group), —COOR12 (R12 is a C1-C2 alkylgroup), —OCOR13 (R13 is a C1-C2 alkyl group), or —COR14 (R14 is a C1-C2alkyl group),

Rg is hydrogen, NH₂, OH, halogen, NO₂, COOH, CN, a C1-C20 alkyl group, aC2-C10 alkenyl group, a C3-C10 cycloalkyl group, a C1-C10 alkoxy group,a C6-C12 aryl, a C5-C12 heterocyclic group, —NR3R4 (R3 is hydrogen, aC1-C20 alkyl or a C6-C12 aryl, R4 is hydrogen, a C1-C20 alkyl or aC6-C12 aryl, and R3 and R4 may be linked to form a heterocycle, furthercontaining at least one hetero atom), —COOR5 (R5 is a C1-C20 alkylgroup, a C6-C12 aryl or a C3-C10 cycloalkyl group), —OCOR6 (R6 is aC1-C20 alkyl group, a C6-C12 aryl or a C3-C10 cycloalkyl group),—NR7CYR8 (Y is O or S, R7 is hydrogen or a C1-C5 alkyl group, and R8 isa C1-C20 alkyl group, a C6-C12 aryl, a C3-C10 cycloalkyl group or aC5-C12 heterocyclic group), —NHS(O)₂R9 (R9 is a C6-C12 aryl or a C5-C12heterocyclic group), or —COR10 (R10 is a C1-C20 alkyl group, a C6-C12aryl, a C3-C10 cycloalkyl group or a C5-C12 heterocyclic group), and

Rh is hydrogen, NH₂, OH, a C1-C5 alkyl group or a C2-C10 alkenyl group,

when Rx is CN,

Ra is hydrogen,

Rb is hydrogen, a C1-C20 alkyl group, a C2-C10 alkenyl group, a C1-C10alkoxy group, —COOR1 (R1 is hydrogen or a C1-C5 alkyl group) or —OCOR2(R2 is a C1-C5 alkyl group),

Rc is OH, NO₂, a C1-C20 alkyl group, a C3-C10 cycloalkyl group, a C2-C10alkoxy group, a C6-C12 aryl, a C5-C12 heterocyclic group, —NR3R4 (R3 ishydrogen, a C1-C20 alkyl group or a C6-C12 aryl, R4 is hydrogen, aC1-C20 alkyl group or a C6-C12 aryl, and R3 and R4 may be linked to forma heterocycle, further containing at least one hetero atom), —COOR5 (R5is a C1-C20 alkyl group, a C6-C12 aryl or a C3-C10 cycloalkyl group),—OCOR6 (R6 is a C1-C20 alkyl group, a C6-C12 aryl or a C3-C10 cycloalkylgroup), —NR7CYR8 (Y is O or S, R7 is hydrogen or a C1-C5 alkyl group,and R8 is a C1-C20 alkyl group, a C6-C12 aryl, a C3-C10 cycloalkyl groupor a C5-C12 heterocyclic group), —NHS(O)₂R9 (R9 is a C6-C12 aryl or aC5-C12 heterocyclic group), or —COR10 (R10 is a C1-C20 alkyl group, aC6-C12 aryl, a C3-C10 cycloalkyl group, or a C5-C12 heterocyclic group),

Rd is hydrogen, halogen, NO₂, COOH, CN, a C2-C20 alkyl group, a C3-C10cycloalkyl group, a C1-C10 alkoxy group, a C6-C12 aryl, a C5-C12heterocyclic group, —NR3R4 (R3 is hydrogen, a C1-C20 alkyl group or aC6-C12 aryl, R4 is hydrogen, a C1-C20 alkyl group or a C6-C12 aryl, andR3 and R4 are linked to form a heterocycle, further containing at leastone hetero atom), —COOR5 (R5 is a C1-C20 alkyl group, a C6-C12 aryl or aC3-C10 cycloalkyl group), —OCOR6 (R6 is a C1-C20 alkyl group, a C6-C12aryl or a C3-C10 cycloalkyl group), —NR7CYR8 (Y is O or S, R7 ishydrogen or a C1-C5 alkyl group, and R8 is a C1-C20 alkyl group, aC6-C12 aryl, a C3-C10 cycloalkyl group or a C5-C12 heterocyclic group),—NHS(O)₂R9 (R9 is a C6-C12 aryl or a C5-C12 heterocyclic group), orCOR10 (R10 is a C1-C20 alkyl group, a C6-C12 aryl, a C3-C10 cycloalkylgroup or a C5-C12 heterocyclic group),

Re is hydrogen, CN, a C2-C20 alkyl group, a C2-C10 alkenyl group, aC1-C10 alkoxy, a C6-C12 aryl, a C5-C12 heterocyclic group, —NR7CYR8 (Yis O or S, R7 is hydrogen or a C1-C5 alkyl group, and R8 is a C1-C20alkyl group, a C6-C12 aryl, a C3-C10 cycloalkyl group or a C5-C12heterocyclic group) or —NHS(O)₂R9 (R9 is a C6-C12 aryl or a C5-C12heterocyclic group),

Rf and Rg are each hydrogen, and

Rh is hydrogen, a C1-C5 alkyl group or a C2-C10 alkenyl group,

the hetero atom of the heterocyclic group may be at least one selectedfrom the group consisting of nitrogen, oxygen and sulfur,

the alkyl group may be substituted with at least one substituentselected from the group consisting of OH, amine, a C6-C12 aryl, a C5-C10heterocyclic group and a C3-C10 cycloalkyl group,

the alkoxy group may be substituted with at least one substituentselected from the group consisting of halogen, a C6-C12 aryl, a C3-C10cycloalkyl group, amine and an aminocarbonyl group,

the heterocyclic group may be substituted with at least one substituentselected from the group consisting of an alkyl group, anamine-substituted alkyl group, amine, an amide group and a carboxylgroup,

the aryl may be substituted with at least one substituent selected fromthe group consisting of halogen, an alkyl group, a hydroxyl group, analkoxy group, a carboxyl group, an ester group, a nitro group and anamine group,

A, B, D, E, G, J, L and M may be linked with an adjacent group to form afused ring, and

Rd cannot be NO₂ when Rb is CH₃.

The compound of the present invention may be synthesized via a varietyof methods, and typically the synthesis process of the case where Rx ofChemical Formula 1 is CN may be different from those of the other cases.

When Rx is CN, the stilbene derivative represented by Chemical Formula 1may be prepared by reacting a phenylacetonitrile derivative representedby Chemical Formula 2 below with a benzaldehyde derivative representedby Chemical Formula 3 below.

The phenylacetonitrile derivative represented by Chemical Formula 2 andthe benzaldehyde derivative represented by Chemical Formula 3 may becommercially available products, or may be used after being preparedthrough methods known in the art.

The above reaction may be carried out in the presence of an organicsolvent, or without any solvent. In this case, the reaction time may bereduced and the yield may be increased using microwaves.

The organic solvent is not limited, but preferably includes an alcohol,and more preferably butanol, methanol, ethanol, or propanol. A catalystsuch as triphenylphosphine, piperidine or the like may be added topromote the reaction.

Rx=CN

In Chemical Formulas 2 and 3,

A, B, D, E, G, J, L, M, Rc and Rd are as defined in A, B, D, E, G, J, L,M, Rc and Rd of Chemical Formula 1.

When Rx is H, CH₃, NH₂, F, Cl, Br or I, the stilbene derivativerepresented by Chemical Formula 1 may be prepared by reacting an olefinderivative represented by Chemical Formula 4 below with an organichalide derivative represented by Chemical Formula 5 below.

The olefin derivative represented by Chemical Formula 4 and the organichalide derivative represented by Chemical Formula 5 may be commerciallyavailable products, or may be used after being prepared throughprocesses known in the art.

The above reaction is preferably carried out using a triethanolamineorganic solvent in the presence of a palladium (II) acetate catalyst.

Rx=H, CH₃, NH₂, F, Cl, Br, I

In Chemical Formulas 4 and 5,

Rx is hydrogen, CH₃, NH₂, F, Cl, Br or I,

X is F, Cl, Br or I, and

A, B, D, E, G, J, L, M, Rc and Rd are as defined in A, B, D, E, G, J, L,M, Rc and Rd of Chemical Formula 1.

The stilbene derivative represented by Chemical Formula 1 according tothe present invention may be used as a preventative or therapeutic agentof cyclophilin-related diseases along with a pharmaceutically acceptablecarrier.

Also, the stilbene derivative represented by Chemical Formula 1according to the present invention may be used as a reference materialfor comparison of efficacy of therapeutic agents for cyclophilin-relateddiseases.

In the present invention, the alkyl group or alkenyl group may be linearor branched.

As used herein, the term “halogen atom” may refer to fluorine, chlorine,bromine or iodine.

In the present invention, when A, B, D, E, G, J, L and M are linked withan adjacent group to form a fused ring, the fused ring is preferably asix-membered ring or a five-membered ring. Furthermore, the fused ringmay contain at least one of hetero atoms such as N, O and S. The fusedring may be furan or thiophene.

In an embodiment of the present invention, A is preferably CRa or N, Bis preferably CRb, G is preferably CRe, J is preferably CRf, M ispreferably CRg or N, and D, E and L are preferably CH, but the presentinvention is not limited thereto.

In another embodiment of the present invention, Rb is preferablyhydrogen or a C1-C8 alkyl group, but the present invention is notlimited thereto.

In still another embodiment of the present invention, Rc is preferably aC1-C20 alkyl group, a C2-C10 alkoxy group, a phenylalkyl group, a nitrogroup, a C3-C10 cycloalkyl group, a C5-C12 heterocyclic group or aC1-C10 alkylketone, but the present invention is not limited thereto.

In yet another embodiment of the present invention, Rd is preferably aC2-C20 alkyl group; a C3-C10 ester group; a C3-C10 cycloalkyl group; acycloalkyl-group-substituted methoxy; an amine-group-substituted ethoxy;a carboxyl group; a phenyl-group-substituted C2-C20 alkyl group, thephenyl group being unsubstituted or substituted with a C1-C5 alkylgroup, a C1-C5 alkoxy group, a carboxyl group or an amine group; amine;N-methylpiperazine; piperidine; morpholine; or —COOR5 (R5 is a C1-C20alkyl group, a C6-C12 aryl or a C3-C10 cycloalkyl group), but thepresent invention is not limited thereto.

In still yet another embodiment of the present invention, Re ispreferably hydrogen, OH, a C1-C20 alkyl group, or a C1-C10 alkoxy group,but the present invention is not limited thereto.

In a further embodiment of the present invention, Rg is preferablyhydrogen, OH, a C1-C20 alkyl group; a C3-C10 ester group; a C3-C10cycloalkyl group; a cycloalkyl-group-substituted methoxy; anamine-group-substituted ethoxy; a phenyl-group-substituted C2-C20 alkylgroup, the phenyl group being unsubstituted or substituted with a C1-C5alkyl group, a C1-C5 alkoxy group, a carboxyl group or an amine group;amine; N-methylpiperazine; piperidine; morpholine; or a carboxyl group,but the present invention is not limited thereto.

In still a further embodiment of the present invention, Rh is preferablyhydrogen, but the present invention is not limited thereto.

In the present invention, the alkyl group may be a substituted orunsubstituted alkyl, such as —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂(CH₂)₂CH₃,—CH₂(CH₂)₃CH₃, —CH(CH₃)CH₂CH₃, —CH₂CH(CH₃)CH₂CH₃, —CH₂CH₂CH(CH₃)₂,—CH(CH₃)₂, —C(CH₃)₃, —CH₂C(CH₃)₃, —CH₂CH(CH₃)₂, —CH(CH₃)CH(CH₃)₂,—CH(CH₃)C(CH₃)₃, —C(CH₃)₂CH₂CH₃, —C(CH₃)₂CH(CH₃)₂, —C(CH₃)₂C(CH₃)₃,—CH₂CH₂C(CH₃)₃, —CH₂CH(CH₃)CH(CH₃)₂, —CH₂CH₂C(CH₃)₂CH₂CH₃,—CH₂CH₂CH(CH₃)CH₂C(CH₃)₃, —CH₂Ph, —CH₂CH₂Ph,

but the present invention is not limited thereto.

In the present invention, the alkoxy group may be a substituted orunsubstituted alkoxy group, such as —OCH₃, —OCF₃, —OCH₂CH₃, —OCH₂CH₂CH₃,—OCH₂CH₂CH₂CH₃, —OCH(CH₃)CH₂CH₃, —OCH₂CONH₂, —OCH₂CH₂N(CH₃)₂,

but the present invention is not limited thereto.

In the present invention, the heterocyclic group may be

but the present invention is not limited thereto.

In the present invention, the —NR3R4 may be —NH₂, —NHCH₃, —N(CH₃)₂,

but the present invention is not limited thereto.

In the present invention, —COOR5 may be COOCH₃, —COOCH₂CH₃,COO(CH₂)₂CH₃, —COO(CH₂)₃CH₃, COO(CH₂)₄CH₃, COOCH(CH₃)₂,

but the present invention is not limited thereto.

In the present invention, —OCOR6 may be

but the present invention is not limited thereto.

In the present invention, the —NR7CYR8 group may be

but the present invention is not limited thereto.

In the present invention, the —NHS(O)₂R9 group may be

but the present invention is not limited thereto.

In the present invention, COR10 may be COC(CH₃)₃, but the presentinvention is not limited thereto.

As used herein, the term “pharmaceutically acceptable carrier” may bedefined as a carrier or diluent that does not impair the biologicalactivity or properties of the composition.

The pharmaceutically acceptable carrier or additive may include at leastone of diluents or excipients such as a stabilizer, a filler, anextender, a wetting agent, a disintegrant, a lubricant, a binder, asurfactant, and the like, which are typically used.

The disintegrant may include agar, starch, alginic acid or a sodium saltthereof, anhydrous calcium hydrogen phosphate, and the like. Thelubricant may include silica, talc, stearic acid or a magnesium salt orcalcium salt thereof, polyethylene glycol, magnesiumaluminometasilicate, and the like. The binder may include magnesiumaluminum silicate, starch paste, gelatin, tragacanth, methylcellulose,sodium carboxymethylcellulose, polyvinylpyrrolidone, low-substitutedhydroxypropylcellulose, and the like.

In addition thereto, lactose, dextrose, sucrose, mannitol, sorbitol,cellulose or glycine may be used as the diluent. In some cases, commonlyknown boiling salts, absorbents, coloring agents, flavoring agents,sweetening agents and the like may be used therewith.

Also, the stabilizer may include a sodium (Na)-free stabilizer, examplesof which include magnesium aluminometasilicate, magnesiumaluminosilicate, magnesium aluminate, dried aluminum hydroxide,synthetic hydrotalcite, synthetic aluminum silicate, magnesiumcarbonate, precipitated calcium carbonate, magnesium oxide, aluminumhydroxide, L-arginine, potassium phosphate, dipotassium hydrogenphosphate, potassium dihydrogen phosphate, ammonium chloride, aluminumchloride, and the like, which may be used alone or in combinations oftwo or more thereof.

A pharmaceutical composition, containing the stilbene derivative ofChemical Formula 1 of the present invention, may be administered in avariety of ways that facilitate administration of the compound into theorganism. The pharmaceutical composition containing the compound of thepresent invention may be administered via oral administration,intrarectal administration, intravaginal administration, intranasaladministration, intraocular administration, intraoral administration,sublingual administration, subcutaneous administration, intramuscularadministration, intravenous administration, intrathecal administration,intradermal administration, epidural administration, and the like.

The pharmaceutical composition, containing the compound of the presentinvention, may be provided in a dosage form of a tablet, capsule,powder, dropping pill, pulvis, bolus, tincture or cataplasm. Thepreferred tablet may be a typical tablet, coated tablet, dispersibletablet, effervescent tablet, etc., or may be a multi-compressed tablet,such as a double tablet, a tablet-in-tablet, a multilayer tablet, etc.

The preferred administration amount of the stilbene derivative orpharmaceutically acceptable salt thereof included in the pharmaceuticalcomposition containing the compound of the present invention variesdepending on the status and body weight of a patient, the severity ofdisease, the type of drug, the administration route and duration, butmay be appropriately selected by those skilled in the art.

A better understanding of the present invention may be achieved via thefollowing non-limiting examples, which are merely set forth toillustrate but are not to be construed as limiting the scope of thepresent invention. The following examples may be appropriately modifiedand altered within the scope of the present invention.

Example 1. Preparation of Stilbene Derivative in which Rx is CN

1) Use of Solvent

1 eq. of a phenylacetonitrile derivative of Chemical Formula 2 and 1.3eq. of a benzaldehyde derivative of Chemical Formula 3 were refluxedwith 0.2 eq. of triphenylphosphine in a butanol solvent, followed by aKnoevenagel condensation reaction, thus yielding a compound of ChemicalFormula 1.

2) Use of Microwaves

1 eq. of a phenylacetonitrile derivative of Chemical Formula 2, 1.3 eq.of a benzaldehyde derivative of Chemical Formula 3 and 0.2 eq. oftriphenylphosphine were treated with microwaves, thus yielding acompound of Chemical Formula 1. When the microwaves are used, thereaction time may be shortened and the yield may be increased.

Example 2. Preparation of Derivative in which Rx is Hydrogen, CH₃, NH₂,F, Cl, Br, I

1 eq. of an olefin derivative of Chemical Formula 4 and 1 eq. of anorganic halide derivative of Chemical Formula 5 were refluxed with 0.01eq. of palladium (II) acetate in a triethanolamine solvent, followed bya Heck olefination reaction, thus yielding a compound of ChemicalFormula 1.

Test Example 1. Evaluation of Cis-Trans Isomerase Inhibitory Activity ofStilbene Derivative

Chymotrypsin cleaves a trans-type alanine-proline peptide bond. WhenSuc-AAPF-pNA (a peptide substrate) and chymotrypsin are mixed, thetrans-type peptide substrate is cleaved and the cis-type peptidesubstrate remains. The remaining cis-type peptide substrate is convertedinto a trans form by a cis-trans isomerase and is then cleaved again bychymotrypsin. When the cis-trans isomerase is present, chymotrypsin isable to cleave a larger amount of trans-type peptide substrate within apredetermined period of time, from which the activity of the cis-transisomerase may be determined. The amount of the cleaved trans-typepeptide substrate is measured using absorbance at 390 nm.

Cyclophilin has cis-trans isomerase activity, and accelerates thecleavage of trans-type peptide substrate by chymotrypsin. When thestilbene derivatives of the present invention were treated together withcyclophilin, the cleavage of the peptide substrate by chymotrypsin wasnot observed to accelerate. Thereby, the stilbene derivatives of theinvention can be concluded to inhibit the activity of cyclophilin.

Compounds 1 to 155 (Tables 1 to 10) below may be grouped as followsbased on the cis-trans isomerase inhibitory activity (IC₅₀) values:

Group A (G_(A)): IC₅₀ of 2000 nM or less but exceeding 200 nM,

Group B (G_(B)): IC₅₀ of 200 nM or less but exceeding 20 nM, and

Group C (G_(C)): IC₅₀ of 20 nM or less.

TABLE 1 A = CRa, B = CRb, G = CRe, J = CRf, D = E = L = M = CH Test Com-Example pound Rx Ra Rb Rc Rd Re Rf 1 3 4 1 CN H H CH₃ N(CH₃)₂ H H G_(A)G_(D) G_(G) 2 CN H H CH₂CH₃ COOH H H G_(A) G_(D) G_(G) 3 CN H H CH₂CH₃N(CH₃)₂ H H G_(A) G_(D) G_(G) 4 CN H H i-Pr Cl H H G_(A) G_(D) G_(G) 5CN H H i-Pr COOH H H G_(A) G_(D) G_(G) 6 CN H H i-Pr OCH₃ H H G_(A)G_(D) G_(G) 7 CN H H NO₂ N(CH₃)₂ H H G_(A) G_(D) G_(G) 8 CN H HCH₂CH₂CH₂CH₃ COOH H H G_(B) G_(E) G_(H) 9 CN H H CH(CH₃)CH₂CH₃ COOH H HG_(B) G_(E) G_(H) 10 CN H H t-Bu COOH H H G_(B) G_(E) G_(H) 11 CN H Ht-Bu OCH₃ H H G_(A) G_(D) G_(G) 12 CN H CH₃ CH₃ OCH₃ H H G_(A) G_(D)G_(G) 13 CN H CH₃ CH₃ COOH H H G_(A) G_(D) G_(G) 14 CN H H COC(CH₃)₃OCH₃ H H G_(B) G_(E) G_(H) 15 CN H H COC(CH₃)₃ COOH H H G_(A) G_(D)G_(G) 16 CN H H OCH₂CH₃ OCH₃ H H G_(A) G_(D) G_(G) 17 CN H H OCH₂CH₃COOH H H G_(A) G_(D) G_(G) 18 CN H H OCH₂CH₂CH₂CH₃ OCH₃ H H G_(B) G_(E)G_(H) 19 CN H H OCH₂CH₂CH₂CH₃ COOH H H G_(B) G_(E) G_(H) 20 CN H H CH₂PhOCH₃ H H G_(C) G_(F) G_(I) 21 CN H H CH₂Ph COOH H H G_(C) G_(F) G_(I) 22CN H H NO₂ CH₂CH₃ H H G_(A) G_(D) G_(G) 23 CN H H NO₂ i-Pro H H G_(A)G_(D) G_(G) 24 CN H H NO₂ NH₂ H H G_(A) G_(D) G_(G) 25 CN H H NO₂

H H G_(A) G_(D) G_(G) 26 CN H H NO₂ OCH(CH₃)CH₂CH₃ H H G_(A) G_(D) G_(G)27 CN H H NO₂

H H G_(B) G_(E) G_(H) 28 CN H H NO₂ OCH₂CH₂N(CH₃)₂ H H G_(A) G_(D) G_(G)29 CN H H NO₂

H H G_(A) G_(D) G_(G) 30 CN H H NO₂

H H G_(A) G_(D) G_(G) 31 CN H H NO₂

H H G_(B) G_(E) G_(H) 32 CN H H NO₂ H OCH₂CH₂CH(CH₃)₂ H G_(A) G_(D)G_(G) 33 CN H H NO₂ H OCH₂CH₂CH₂N(CH₃)₂ H G_(A) G_(D) G_(G) 34 CN H HNO₂ CH₂CH(CH₃)₂ H H G_(A) G_(D) G_(G) 35 CN H H NO₂ CH₂C(CH₃)₃ H H G_(B)G_(E) G_(H) 36 CN H H NO₂ CH₂CH₂CH(CH₃)₂ H H G_(B) G_(E) G_(H) 37 CN H HNO₂

H H G_(B) G_(E) G_(H) 38 CN H H NO₂ CH₂CH₂Ph H H G_(B) G_(E) G_(H) 39 CNH H NO₂

H H G_(C) G_(F) G_(I) 40 CN H H NO₂

H H G_(C) G_(F) G_(I) 41 CN H H NO₂

H H G_(C) G_(F) G_(I) 42 CN H H NO₂ CH₂CH₂CH₂Ph H H G_(A) G_(D) G_(G) 43CN H H NO₂ CH₂CH₂C(CH₃)₃ H H G_(B) G_(E) G_(H) 44 CN H H NO₂

H H G_(B) G_(E) G_(H) 45 CN H H NO₂

H H G_(B) G_(E) G_(H) 46 CN H H NO₂

H H G_(B) G_(E) G_(H) 47 CN H H NO₂

H H G_(B) G_(E) G_(H) 48 CN H H NO₂

H H G_(B) G_(E) G_(H) 49 CN H H NO₂

H H G_(A) G_(D) G_(G) 51 CN H H NO₂

H H G_(A) G_(D) G_(G) 52 CN H H NO₂

H H G_(B) G_(E) G_(H) 53 CN H H NO₂

H H G_(B) G_(E) G_(H) 54 CN H H CH₂C(CH₃)₃ COOH H H G_(C) G_(F) G_(I) 55CN H H

COOH H H G_(B) G_(E) G_(H) 56 CN H H

COOH H H G_(B) G_(E) G_(H) 57 CN H H

COOH H H G_(C) G_(F) G_(I) 58 CN H H

COOH H H G_(B) G_(E) G_(H) 59 CN H H

COOH H H G_(C) G_(F) G_(I) 60 CN H H

COOH H H G_(C) G_(F) G_(I) 61 CN H H

COOH H H G_(C) G_(F) G_(I) 62 CN H H

COOH H H G_(C) G_(F) G_(I) 63 CN H H

COOH H H G_(B) G_(E) G_(H) 64 H H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H H G_(C)G_(F) G_(I) 65 H H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ CH₃ H G_(B) G_(E) G_(H) 66H H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ CH₂CH₃ H G_(B) G_(E) G_(H) 67 H CH₃ HCH₂C(CH₃)₃ COO(CH₂)₃CH₃ H H G_(B) G_(E) G_(H) 68 H CH₂CH₃ H CH₂C(CH₃)₃COO(CH₂)₃CH₃ H H G_(B) G_(E) G_(H) 69 H H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ HCH₃ G_(B) G_(E) G_(H) 70 H H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ CH₃ CH₃ G_(B)G_(E) G_(H) 71 H H H CH₂C(CH₃)₃ COO(CH₂)₂CH₃ H H G_(C) G_(F) G_(I) 72 HH H CH₂C(CH₃)₃ COO(CH₂)₄CH₃ H H G_(C) G_(F) G_(I) 73 H H H CH₂C(CH₃)₃COOCH(CH3)₂ H H G_(C) G_(F) G_(I) 74 H H H CH₂C(CH₃)₃

H H G_(C) G_(F) G_(I) 75 H H H CH₂C(CH₃)₃

H H G_(B) G_(E) G_(H) 76 H H H CH₂C(CH₃)₃ COOCH₂Ph H H G_(C) G_(F) G_(I)77 H H H CH₂C(CH₃)₃

H H G_(B) G_(E) G_(H) 78 H H H CH₂CH(CH₃)CH₂CH₃ COO(CH₂)₃CH₃ H H G_(B)G_(E) G_(H) 79 H H H

COO(CH₂)₃CH₃ H H G_(B) G_(E) G_(H) 80 H H H

COO(CH₂)₃CH₃ H H G_(B) G_(E) G_(H) 81 H H H

COO(CH₂)₃CH₃ H H G_(B) G_(E) G_(H) 82 CH₃ H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ HH G_(B) G_(E) G_(H) 83 CH₃ H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ CH₃ H G_(B) G_(E)G_(H) 84 CH₃ CH₃ H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H H G_(B) G_(E) G_(H) 85 CH₃H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H CH₃ G_(B) G_(E) G_(H) 86 CH₃ H HCH₂C(CH₃)₃ COO(CH₂)₃CH₃ CH₃ CH₃ G_(B) G_(E) G_(H) 87 CH₃ H H CH₂C(CH₃)₃COO(CH₂)₂CH₃ H H G_(B) G_(E) G_(H) 88 CH₃ H H CH₂C(CH₃)₃ COO(CH₂)₄CH₃ HH G_(B) G_(E) G_(H) 89 CH₃ H H CH₂C(CH₃)₃ COOCH(CH₃)₂ H H G_(B) G_(E)G_(H) 90 CH₃ H H CH₂C(CH₃)₃

H H G_(B) G_(E) G_(H) 91 CH₃ H H CH₂C(CH₃)₃

H H G_(B) G_(E) G_(H) 92 CH₃ H H CH₂C(CH₃)₃ COOCH₂Ph H H G_(B) G_(E)G_(H) 93 CH₃ H H CH₂C(CH₃)₃

H H G_(B) G_(E) G_(H) 94 CH₃ H H CH₂CH(CH₃)CH₂CH₃ COO(CH₂)₃CH₃ H H G_(B)G_(E) G_(H) 95 CH₃ H H

COO(CH₂)₃CH₃ H H G_(B) G_(E) G_(H) 96 CH₃ H H

COO(CH₂)₃CH₃ H H G_(B) G_(E) G_(H) 97 CH₃ H H

COO(CH₂)₃CH₃ H H G_(B) G_(E) G_(H) 98 NH₂ H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ HH G_(B) G_(E) G_(H) 99 NH₂ H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ CH₃ H G_(B) G_(E)G_(H) 100 NH₂ CH₃ H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H H G_(B) G_(E) G_(H) 101NH₂ H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H CH₃ G_(B) G_(E) G_(H) 102 NH₂ H HCH₂C(CH₃)₃ COO(CH₂)₃CH₃ CH₃ CH₃ G_(B) G_(E) G_(H) 103 NH₂ H H CH₂C(CH₃)₃COO(CH₂)₄CH₃ H H G_(B) G_(E) G_(H) 104 NH₂ H H CH₂C(CH₃)₃ COOCH(CH₃)₂ HH G_(B) G_(E) G_(H) 105 NH₂ H H CH₂C(CH₃)₃

H H G_(B) G_(E) G_(H) 106 NH₂ H H CH₂C(CH₃)₃ COOCH₂Ph H H G_(B) G_(E)G_(H) 107 NH₂ H H CH₂C(CH₃)₃

H H G_(B) G_(E) G_(H) 108 NH₂ H H CH₂CH(CH₃)CH₂CH₃ COO(CH₂)₃CH₃ H HG_(B) G_(E) G_(H) 109 NH₂ H H

COO(CH₂)₃CH₃ H H G_(B) G_(E) G_(H) 110 NH₂ H H

COO(CH₂)₃CH₃ H H G_(B) G_(E) G_(H) 111 NH₂ H H

COO(CH₂)₃CH3 H H G_(B) G_(E) G_(H) 112 F H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H HG_(C) G_(F) G_(I) 113 Cl H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ CH₃ H G_(C) G_(F)G_(I) 114 Br CH₃ H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H H G_(C) G_(F) G_(I) 115 I HH CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H CH₃ G_(C) G_(F) G_(I) 116 F H H CH₂C(CH₃)₃COO(CH₂)₃CH₃ CH₃ CH₃ G_(C) G_(F) G_(I) 117 Cl H H CH₂C(CH₃)₃COO(CH₂)₄CH₃ H H G_(C) G_(F) G_(I) 118 Br H H CH₂C(CH₃)₃ COOCH(CH3)₂ H HG_(C) G_(F) G_(I) 119 I H H CH₂C(CH₃)₃

H H G_(C) G_(F) G_(I) 120 F H H CH₂C(CH₃)₃ COOCH₂Ph H H G_(C) G_(F)G_(I) 121 Cl H H CH₂C(CH₃)₃

H H G_(C) G_(F) G_(I) 122 Br H H CH₂CH(CH₃)CH₂CH₃ COO(CH₂)₃CH₃ H H G_(B)G_(E) G_(H) 123 I H H

COO(CH₂)₃CH₃ H H G_(B) G_(E) G_(H) 124 H H H CH₂C(CH₃)₃ COOCH₃ H H G_(C)G_(F) G_(I) 125 H H H CH₂CH(CH₃)CH₂CH₃ COOCH₃ H H G_(B) G_(E) G_(H) 126H H H

COOCH₃ H H G_(B) G_(E) G_(H) 127 H H H

COOCH₃ H H G_(B) G_(E) G_(H) 128 H H H

COOCH₃ H H G_(B) G_(E) G_(H) 129 H H H

COOCH₃ H H G_(B) G_(E) G_(H) 130 H H H CH₂(CH₂)₃CH₃ COOCH₃ H H G_(C)G_(F) G_(I) 131 H H H

COO(CH₂)₃CH₃ H H G_(C) G_(F) G_(I) 132 H H H CH₂(CH₂)₃CH₃ COO(CH₂)3CH₃ HH G_(C) G_(F) G_(I) 133 H H H CH₂(CH₃)₃

H H G_(B) G_(E) G_(H) 134 H H H CH₂C(CH₃)₃ COOH H H G_(C) G_(F) G_(I)135 H H H CH₂C(CH₃)₃ COOH OH H G_(C) G_(F) G_(I) 136 H H H CH₂C(CH₃)₃COOH H OH G_(C) G_(F) G_(I) 137 H H H CH₂C(CH₃)₃ COOH NH₂ H G_(C) G_(F)G_(I) 138 H H H CH₂C(CH₃)₃ COOH H NH₂ G_(C) G_(F) G_(I) 139 H H HCH₂C(CH₃)₃ COOH CH₃ H G_(C) G_(F) G_(I) 140 H H H CH₂C(CH₃)₃ COOH H CH₃G_(C) G_(F) G_(I) 141 H H H CH₂C(CH₃)₃ CONH₂ H H G_(C) G_(F) G_(I)

TABLE 2 A = CRa, B = CRb, G = CRe, D = E = M = CH Fused ring Com-formation Test Example pound R_(x) R_(a) R_(b) R_(c) R_(d) R_(e) of Jand L 1 3 4 142 H H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H

GB GE GH

TABLE 3 A = N, B = CRb, G = CRe, J = CRf, D = E = L = M = CH TestExample Compound R_(x) R_(b) R_(c) R_(d) R_(e) R_(f) 1 3 4 143 H HCH₂C(CH₃)₃ COO(CH₂)₃CH₃ H H G_(B) G_(E) G_(H)

TABLE 4 A = CRa, B = N, G = CRe, J = CRf, D = E = L = M = CH TestExample Compound R_(x) R_(a) R_(c) R_(d) R_(e) R_(f) 1 3 4 144 H HCH₂C(CH₃)₃ COO(CH₂)₃CH₃ H H G_(B) G_(E) G_(H)

TABLE 5 A = CRa, B = CRb, G = N, J = CRf, D = E = L = M = CH TestExample Compound R_(x) R_(a) R_(b) R_(c) R_(d) R_(f) 1 3 4 145 H H HCH₂C(CH₃)₃ COO(CH₂)₃CH₃ H G_(B) G_(E) G_(H)

TABLE 6 A = CRa, B = CRb, G = CRe, J = N, D = E = L = M = CH TestExample Compound R_(x) R_(a) R_(b) R_(c) R_(d) R_(e) 1 3 4 146 H H HCH₂C(CH₃)₃ COO(CH₂)₃CH₃ H G_(B) G_(E) G_(H)

TABLE 7 A = CRa, B = CRb, G = CRe, J = CRf, D = E = M = CH, L = N TestExample Compound R_(x) R_(a) R_(b) R_(c) R_(d) R_(e) R_(f) 1 3 4 147 H HH CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H H G_(B) G_(E) G_(H)

TABLE 8 A = CRa, B = CRb, G = CRe, J = CRf, D = E = L = CH, M = N TestExample Compound R_(x) R_(a) R_(b) R_(c) R_(d) R_(e) R_(f) 1 3 4 148 H HH CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H H G_(B) G_(E) G_(H)

TABLE 9 A = CRa, B = CRb, G = CRe, J = CRf, M = CRg, D = E = L = CH TestExample Compound Rx Ra Rb Rc Rd Re Rf Rg 1 3 4 149 H H H CH₂C(CH₃)₃COO(CH₂)₃CH₃ H H COO(CH₂)₃CH₃ G_(B) G_(E) G_(H) 150 H H H CH₂C(CH₃)₃COOH H H OH G_(C) G_(F) G_(I) 151 H H H CH₂C(CH₃)₃ COOH H H NH₂ G_(C)G_(F) G_(I) 152 H H H CH₂C(CH₃)₃ COOH H H CH₃ G_(C) G_(F) G_(I)

TABLE 10 A = CRa, B = CRb, G = CRe, J = CRf, L = CRh, D = E = M = CHTest Example Compound Rx Ra Rb Rc Rd Re Rf Rh 1 3 4 153 H H H CH₂C(CH₃)₃COOH H H OH G_(B) G_(E) G_(H) 154 H H H CH₂C(CH₃)₃ COOH H H NH₂ G_(B)G_(E) G_(H) 155 H H H CH₂C(CH₃)₃ COOH H H CH₃ G_(B) G_(E) G_(H)

Test Example 2. Evaluation of Cytotoxicity of Stilbene Derivative

The cytotoxicity of the stilbene derivatives was measured. Repliconcells that stably replicate a hepatitis C virus genome were attached toa 96-well plate and cultured in a CO₂ incubator at 37° C. for 24 hr. Thereplicon cells cultured for one day were washed with a phosphatebuffered saline (PBS) solution, treated with the compounds of thepresent invention, and then cultured for 72 hr. Thereafter, through theMTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]cytotoxicity test, CC₅₀ values of the compounds of the present inventionwere measured. The CC₅₀ values of the compounds of the present inventionwere 200 μM or more. For example, Compound 64 had a CC₅₀ of 320 μM,Compound 65 had a CC₅₀ of 284 μM, and Compound 66 had a CC₅₀ of 245 μM.Accordingly, the compounds of Chemical Formula 1 of the presentinvention exhibited no cytotoxicity.

Test Example 3. Evaluation of Antiviral Activity of Stilbene Derivative

The antiviral activity of the stilbene derivatives on hepatitis C viruswas measured. The replicon cells that stably replicate the hepatitis Cvirus genome were attached to a culture plate and cultured in a CO₂incubator at 37° C. for 24 hr. The replicon cells cultured for one daywere washed with a PBS solution, treated with the compounds of thepresent invention, and then cultured for 72 hr. The stilbenederivative-treated replicon cells were washed with a cold PBS solutionand added with 20 μL of a cell lysis solution so that the cells werelysed in ice for 20 min. 100 μL of a Renilla luciferase substrate wasadded thereto, after which the luminescence thereof was measured andthus the amount of the hepatitis C virus genome was estimated. Theamount of the hepatitis C virus genome in the stilbenederivative-treated replicon cells according to the present inventionrelative to the amount of the hepatitis C virus genome indimethylsulfoxide (DMSO)-treated replicon cells is shown.

Compounds 1 to 155 of Tables 1 to 10 may be grouped as follows based onthe antiviral activity (EC₅₀) values:

Group D (G_(D)): EC₅₀ of 50 μM or less but exceeding 5 μM,

Group E (G_(E)): EC₅₀ of 5 μM or less but exceeding 0.5 μM, and

Group F (G_(F)): EC₅₀ of 0.5 μM or less.

Thus, the compounds of Chemical Formula 1 of the present inventionexhibited antiviral effects.

Test Example 4. Inhibitory Activity Test on Mitochondrial Swelling

Cyclophilin is a key protein for forming permeability transition pores(PTP) in mitochondria. When permeability transition pores are formed,mitochondria swell, whereby the outer membrane thereof ruptures and thuscell death progresses. Such mitochondrial dysfunction causes manydiseases including neurodegenerative diseases, cancer, and the like.Cyclosporine, a known cyclophilin inhibitor, is capable of preventingthe formation of permeability transition pores to thus suppressmitochondrial swelling.

The mitochondrial swelling test was performed as follows. Specifically,the hepatocytes were disrupted using a Dounce tissue grinder. Thedisrupted cells were centrifuged at 700×g for 10 min and the supernatantwas transferred into a new tube. The supernatant was centrifuged at12,000×g for 15 min, thereby obtaining mitochondria.

When the extracted mitochondria were added with calcium, they swelled,which may be observed by measuring the absorbance at 520 nm. Thestilbene derivatives are effective at inhibiting mitochondrial swellingdue to calcium.

The activity of Compounds 1 to 155 of Tables 1 to 10 on inhibitingmitochondrial swelling may be determined based on IC₅₀ values, and maybe grouped as follows:

Group G (G_(G)): IC₅₀ of 500 μM or less but exceeding 50 μM,

Group H (G_(H)): IC₅₀ of 50 μM or less but exceeding 5 μM, and

Group I (G_(I)): IC₅₀ of 5 μM or less.

The results of NMR analysis and LCMS analysis of Compounds 1 to 155corresponding to the stilbene derivatives prepared in Examples 1 and 2are as follows.

Compound 1:

NMR (400 MHz, CDCl₃): 8.03 (d, 1H), 7.84 (s, 1H), 7.63 (d, 2H), 7.37 (m,1H) 7.27 (m, 2H), 7.10 (m, 2H), 2.78 (s, 6H), 2.42 ppm (s, 3H)

LCMS: MH⁺=263.1

Compound 2:

NMR (400 MHz, DMSO-D₆): 8.41 (s, 1H), 8.05 (d, 1H), 7.78 (m, 2H), 7.62(m, 3H) 7.36 (d, 2H), 2.65 (m, 2H), 1.20 ppm (m, 3H)

LCMS: MH⁺=260.1

Compound 3:

NMR (400 MHz, CDCl₃): 8.03 (d, 1H), 7.85 (s, 1H), 7.66 (d, 2H), 7.38 (m,1H) 7.28 (m, 2H), 7.12 (m, 2H), 2.78 (s, 6H), 2.70 (m, 2H), 1.28 ppm (m,3H)

LCMS: MNa⁺=300.1

Compound 4:

NMR (400 MHz, CDCl₃): 8.11 (m, 1H), 7.87 (s, 1H), 7.65 (d, 2H), 7.47 (d,1H) 7.39 (m, 2H), 7.27 (s, 2H), 2.98 (m, 1H), 1.29 ppm (d, 6H)

LCMS: MH⁺=282.0

Compound 5:

NMR (400 MHz, CDCl₃): 8.33 (s, 1H), 8.24 (m, 1H), 7.91 (d, 1H), 7.72 (m,1H) 7.67 (d, 2H), 7.56 (m, 1H), 7.33 (d, 2H), 2.98 (m, 1H), 1.29 ppm (d,6H)

LCMS: MNa⁺=314.1

Compound 6:

NMR (400 MHz, CDCl₃): 8.13 (d, 1H), 7.93 (s, 1H), 7.63 (m, 2H), 7.41 (m,1H) 7.31 (m, 2H), 7.27 (m, 1H), 6.94 (d, 1H), 3.89 (s, 3H), 2.97 (m,1H), 1.28 ppm (d, 6H)

LCMS: MH⁺=278.1

Compound 7:

NMR (400 MHz, CDCl₃): 8.31 (m, 2H), 8.10 (m, 2H), 7.91 (d, 2H), 7.44 (m,1H) 7.14 (m, 2H), 2.80 ppm (s, 6H)

LCMS: MH⁺=294.1

Compound 8:

NMR (400 MHz, DMSO-D₆): 8.41 (s, 1H), 8.04 (m, 1H), 7.76 (m, 2H), 7.62(m, 3H) 7.35 (d, 2H), 2.63 (m, 2H), 1.58 (m, 2H), 1.32 (m, 2H), 0.92 ppm(m, 3H)

LCMS: MH⁺=304.1

Compound 9:

NMR (400 MHz, CDCl₃): 8.33 (s, 1H), 8.23 (d, 1H), 7.92 (d, 1H), 7.73 (m,1H) 7.67 (d, 2H), 7.56 (m, 1H), 7.28 (m, 2H), 2.67 (m, 1H), 1.66 (m,2H), 1.28 (d, 3H), 0.860 ppm (m, 3H)

LCMS: MNa⁺=288.1

Compound 10:

NMR (400 MHz, CDCl₃): 8.34 (s, 1H), 8.23 (m, 1H), 7.92 (d, 1H), 7.73 (d,1H) 7.68 (d, 2H), 7.49 (m, 1H), 7.27 (s, 2H), 1.37 ppm (s, 9H)

LCMS: MNa⁺=328.3

Compound 11:

NMR (400 MHz, CDCl₃): 8.15 (d, 1H), 7.95 (s, 1H), 7.64 (d, 2H), 7.46 (d,2H) 7.27 (s, 1H), 7.07 (m, 1H), 6.94 (d, 1H), 3.89 (s, 3H), 1.36 ppm (s,9H)

LCMS: MH⁺=292.2

Compound 12:

NMR (300 MHz, CDCl₃): 7.83 (d, 1H), 7.53 (m, 1H), 7.40 (m, 1H), 7.31 (d,1H) 7.16 (m, 2H), 7.08 (d, 2H), 3.70 (s, 3H), 2.30 ppm (d, 6H)

LCMS: MH⁺=264.1

Compound 13:

NMR (300 MHz, CDCl₃): 7.85 (d, 1H), 7.49 (m, 1H), 7.37 (m, 1H), 7.28 (d,1H) 7.15 (m, 2H), 7.02 (d, 2H), 2.28 ppm (d, 6H)

LCMS: MNa⁺=299.1

Compound 14:

NMR (300 MHz, CDCl₃): 7.58 (d, 2H), 7.55 (d, 1H), 7.36 (m, 1H), 7.32 (d,1H) 7.01 (m, 2H), 6.91 (d, 2H), 3.89 (s, 3H), 1.38 ppm (s, 9H)

LCMS: MH⁺=320.2

Compound 15:

NMR (300 MHz, CDCl₃): 7.75 (d, 1H), 7.72 (m, 2H), 7.65 (d, 2H), 7.61 (d,1H) 7.43 (d, 2H), 7.39 (s, 1H), 1.37 ppm (s, 9H)

LCMS: MNa⁺=355.1

Compound 16:

NMR (300 MHz, CDCl₃): 7.83 (d, 1H), 7.80 (s, 1H), 7.75 (d, 2H), 7.60 (m,1H) 7.25 (d, 1H), 7.19 (m, 1H), 7.08 (d, 2H), 4.12 (m, 2H), 3.89 (s,3H), 1.42 ppm (m, 3H)

LCMS: MH⁺=280.1

Compound 17:

NMR (300 MHz, CDCl₃): 7.94 (d, 1H), 7.90 (s, 1H), 7.83 (d, 2H), 7.65 (m,1H) 7.30 (d, 1H), 7.22 (m, 1H), 7.14 (d, 2H) 4.17 (m, 2H), 1.43 ppm (m,3H)

LCMS: MNa⁺=315.1

Compound 18:

NMR (300 MHz, CDCl₃): 7.82 (d, 1H), 7.67 (s, 1H), 7.55 (m, 1H), 7.50 (d,2H) 7.17 (m, 2H), 6.97 (m, 2H), 3.92 (m, 2H), 3.63 (s, 3H), 1.77 (m,2H), 1.50 (m, 2H), 0.99 ppm (m, 3H)

LCMS: MH⁺=308.2

Compound 19:

NMR (300 MHz, CDCl₃): 7.90 (d, 1H), 7.79 (s, 1H), 7.60 (m, 1H), 7.53 (d,2H) 7.24 (m, 2H), 7.04 (m, 2H), 4.02 (m, 2H), 1.83 (m, 2H0, 1.57 (m,2H), 1.01 ppm (m, 3H)

LCMS: MNa⁺=343.1

Compound 20:

NMR (300 MHz, CDCl₃): 7.84 (d, 1H), 7.81 (s, 1H), 7.75 (m, 3H), 7.59 (m,1H) 7.26 (m, 3H), 7.20 (m, 4H), 7.09 (m, 1H), 4.04 (s, 2H), 3.89 ppm (s,3H)

LCMS: MH⁺=326.2

Compound 21:

NMR (300 MHz, CDCl₃): 7.86 (d, 1H), 7.82 (s, 1H), 7.78 (m, 3H), 7.59 (m,1H) 7.28 (m, 3H), 7.23 (m, 4H), 7.11 (m, 1H), 4.09 ppm (s, 2H)

LCMS: MNa⁺=361.1

Compound 22:

NMR (300 MHz, CDCl₃): 8.23 (d, 2H), 8.15 (s, 1H), 7.83 (d, 2H), 7.67 (m,1H) 7.53 (m, 2H), 7.38 (m, 1H), 2.76 (m, 2H), 1.23 ppm (m, 3H)

LCMS: MH⁺=279.1

Compound 23:

NMR (300 MHz, CDCl₃): 8.22 (d, 2H), 8.16 (s, 1H), 7.84 (d, 2H), 7.66 (m,1H) 7.53 (m, 2H), 7.37 (m, 1H), 2.96 (m, 1H), 1.24 ppm (d, 6H)

LCMS: MH⁺=293.1

Compound 24:

NMR (300 MHz, CDCl₃): 8.30 (d, 1H), 7.57 (d, 1H), 7.50 (s, 1H), 7.35 (m,2H) 6.78 (m, 2H), 6.69 (m, 2H), 6.15 ppm (s, 2H)

LCMS: MH⁺=266.1

Compound 25:

NMR (300 MHz, CDCl₃): 8.36 (d, 2H), 8.16 (d, 1H), 8.13 (s, 1H), 7.91 (d,2H) 7.52 (m, 1H), 7.25 (d, 1H), 7.19 (d, 1H), 3.07 (m, 4H), 2.62 (broads, 4H), 2.41 ppm (s, 3H)

LCMS: MH⁺=349.2

Compound 26:

NMR (300 MHz, CDCl₃): 8.29 (d, 2H), 8.23 (m, 2H), 7.84 (d, 2H), 7.48 (m,1H) 7.07 (m, 1H), 7.00 (m, 1H), 4.50 (m, 1H), 1.86 (m, 2H), 1.39 (d,3H), 1.07 ppm (m, 3H)

LCMS: MH⁺=323.1

Compound 27:

NMR (300 MHz, CDCl₃): 8.38 (d, 2H), 8.28 (m, 1H), 8.24 (s, 1H), 7.88 (d,2H) 7.64 (m, 1H), 6.84 (m, 1H), 6.69 (d, 1H), 3.93 (d, 2H), 0.92 (m,1H), 0.72 (m, 2H), 0.42 ppm (m, 2H)

LCMS: MH⁺=339.1

Compound 28:

NMR (300 MHz, CDCl₃): 8.34 (d, 2H), 8.26 (d, 1H), 8.20 (s, 1H), 7.88 (d,2H) 7.50 (m, 1H), 7.13 (m, 1H), 7.03 (d, 1H), 4.15 (m, 2H), 2.53 (m,2H), 2.31 ppm (s, 6H)

LCMS: MH⁺=338.1

Compound 29:

NMR (300 MHz, CDCl₃): 8.35 (d, 2H), 8.17 (d, 1H), 8.14 (s, 1H), 7.92 (d,2H) 7.48 (m, 1H), 7.18 (m, 2H), 2.98 (m, 4H), 1.74 ppm (m, 6H)

LCMS: MH⁺=334.2

Compound 30:

NMR (300 MHz, CDCl₃): 8.36 (d, 2H), 8.18 (d, 1H), 8.15 (s, 1H), 7.91 (d,2H) 7.55 (m, 1H), 7.26 (m, 1H), 7.19 (d, 1H), 3.89 (m, 4H), 3.03 ppm (m,4H)

LCMS: MH⁺=336.1

Compound 31:

NMR (300 MHz, CDCl₃): 8.35 (d, 2H), 8.10 (s, 1H), 7.89 (m, 3H), 7.46 (m,3H) 2.72 (m, 1H), 1.87 (m, 4H), 1.60 ppm (m, 6H)

LCMS: MH⁺=333.2

Compound 32:

NMR (300 MHz, CDCl₃): 8.34 (d, 2H), 7.88 (d, 2H), 7.68 (s, 1H), 7.56 (s,1H) 7.46 (m, 2H), 7.08 (d, 1H), 4.10 (m, 2H), 1.92 (m, 1H), 1.88 (m,2H), 1.02 ppm (d, 6H)

LCMS: MH⁺=337.2

Compound 33:

NMR (300 MHz, CDCl₃): 8.27 (d, 2H), 7.82 (d, 2H), 7.64 (s, 1H), 7.52 (s,1H) 7.41 (m, 3H), 4.07 (m, 2H), 2.48 (m, 2H), 2.28 (d, 6H), 2.03 ppm (m,2H)

LCMS: MH⁺=352.2

Compound 34:

NMR (300 MHz, CDCl₃): 8.34 (d, 2H), 8.02 (d, 2H), 7.88 (d, 2H), 7.46 (m,2H) 7.36 (m, 1H), 2.65 (d, 2H), 1.86 (m, 1H), 0.96 ppm (d, 6H)

LCMS: MH⁺=307.1

Compound 35:

NMR (400 MHz, CDCl₃): 8.36 (m, 3H), 8.05 (d, 1H), 7.94 (d, 1H), 7.87 (d,2H) 7.75 (d, 1H), 7.45 (m, 2H), 2.68 (s, 2H), 0.94 ppm (s, 9H)

LCMS: MH⁺=321.2

Compound 36:

NMR (300 MHz, CDCl₃): 8.35 (d, 2H), 8.02 (d, 2H), 7.90 (d, 2H), 7.39 (m,3H) 2.76 (m, 2H), 1.67 (m, 1H), 1.52 (m, 2H), 0.98 ppm (d, 6H)

LCMS: MH⁺=321.2

Compound 37:

NMR (400 MHz, CDCl₃): 8.30 (m, 3H), 7.87 (s, 1H), 7.75 (d, 2H), 7.63 (m,2H) 7.53 (m, 2H), 7.08 (d, 2H), 3.98 ppm (s, 2H)

LCMS: MH⁺=409.0

Compound 38:

NMR (400 MHz, CDCl₃): 8.29 (m, 3H), 7.88 (s, 1H), 7.75 (d, 2H), 7.63 (m,2H) 7.54 (m, 2H), 7.24 (m, 2H), 7.06 (d, 2H), 3.07 (m, 2H), 2.96 ppm (m,2H)

LCMS: MH⁺=355.1

Compound 39:

NMR (300 MHz, CDCl₃): 8.34 (d, 2H), 8.27 (d, 1H), 8.02 (d, 2H), 7.88 (d,2H) 7.46 (m, 1H), 7.35 (m, 1H), 2.77 (m, 2H), 1.83 (m, 5H), 1.55 (m,2H), 1.34 (m, 4H), 1.02 ppm (m, 2H)

LCMS: MH⁺=361.2

Compound 40:

NMR (300 MHz, CDCl₃): 8.38 (d, 2H), 8.26 (d, 1H), 8.02 (d, 2H), 7.88 (d,2H), 7.43 (m, 1H), 7.36 (m, 1H), 2.73 (m, 2H), 1.67 (m, 8H), 1.27 (m,3H), 1.16 (m, 2H), 1.04 ppm (m, 2H)

LCMS: MH⁺=375.2

Compound 41:

NMR (300 MHz, CDCl₃): 8.36 (d, 2H), 8.03 (d, 2H), 7.87 (d, 2H), 7.42 (m,3H), 2.65 (d, 2H), 1.89 (m, 1H), 1.72 ppm (m, 10H)

LCMS: MH⁺=347.2

Compound 42:

NMR (300 MHz, CDCl₃): 8.33 (d, 2H), 8.02 (d, 1H), 7.79 (s, 1H), 7.70 (d,2H) 7.47 (m, 1H), 7.40 (d, 2H), 7.30 (m, 5H), 2.7 (m, 4H), 1.99 ppm (m,2H)

LCMS: MH⁺=369.2

Compound 43:

NMR (300 MHz, CDCl₃): 8.37 (d, 2H), 8.03 (d, 2H), 7.88 (d, 2H), 7.46 (m,1H) 7.35 (m, 2H), 2.72 (m, 2H), 1.49 (m, 2H), 1.00 ppm (s, 9H)

LCMS: MH⁺=335.2

Compound 44: LCMS: MH⁺=385.2

Compound 45: LCMS: MH⁺=411.2

Compound 46: LCMS: MH⁺=389.1

Compound 47: LCMS: MH⁺=389.1

Compound 48: LCMS: MH⁺=389.1

Compound 49: LCMS: MH⁺=385.2

Compound 50: LCMS: MH⁺=385.2

Compound 51: LCMS: MNa⁺=420.1

Compound 52: LCMS: MH⁺=369.2

Compound 53: LCMS: MH⁺=370.2

Compound 54:

NMR (300 MHz, CDCl₃): 7.99 (d, 1H), 7.82 (s, 1H), 7.61 (d, 2H), 7.32 (m,1H) 7.25 (m, 2H), 7.12 (m, 2H), 2.21 (s, 2H), 0.97 ppm (s, 9H)

LCMS: MH⁺=320.1

Compound 55:

NMR (300 MHz, CDCl₃): 8.23 (d, 2H), 7.81 (d, 2H), 7.61 (s, 1H), 7.50 (s,1H) 7.39 (m, 3H), 2.77 (m, 1H), 2.08 (m, 1H), 1.22 (s, 3H), 0.76 ppm (m,6H)

LCMS: MH⁺=320.1

Compound 56:

NMR (300 MHz, CDCl₃): 8.19 (d, 1H), 7.83 (s, 1H), 7.63 (d, 2H), 7.54 (m,1H) 7.45 (m, 2H), 7.37 (m, 2H), 2.99 (m, 1H), 1.32 (m, 3H), 1.03 ppm (s,9H)

LCMS: MH⁺=334.1

Compound 57:

NMR (300 MHz, CDCl₃): 8.31 (s, 1H), 8.23 (m, 1H), 7.94 (d, 1H), 7.71 (m,1H) 7.68 (d, 2H), 7.53 (m, 1H), 7.34 (d, 2H), 2.88 (m, 2H), 1.69 (m,2H), 0.98 ppm (s, 9H)

LCMS: MH⁺=334.1

Compound 58:

NMR (300 MHz, CDCl₃): 8.26 (d, 2H), 7.87 (d, 2H), 7.61 (s, 1H), 7.55 (s,1H) 7.40 (m, 3H), 2.67 (m, 2H), 2.08 (m, 1H), 1.88 (m, 1H), 0.96 ppm (m,9H)

LCMS: MH⁺=334.1

Compound 59:

NMR (300 MHz, CDCl₃): 8.35 (s, 1H), 8.24 (m, 1H), 7.91 (d, 1H), 7.73 (m,1H) 7.66 (d, 2H), 7.57 (m, 1H), 7.38 (d, 2H), 2.65 (d, 2H), 1.77 (m,1H), 1.71 ppm (m, 10H)

LCMS: MH⁺=346.1

Compound 60:

NMR (300 MHz, CDCl₃): 8.33 (s, 1H), 8.22 (m, 1H), 7.92 (d, 1H), 7.74 (m,1H) 7.67 (d, 2H), 7.56 (m, 1H), 7.36 (d, 2H), 2.71 (s, 2H), 1.67 (m,8H), 1.29 (m, 3H), 1.17 (m, 2H), 1.06 ppm (m, 2H)

LCMS: MH⁺=360.1

Compound 61:

NMR (300 MHz, CDCl₃): 8.32 (s, 1H), 8.20 (m, 1H), 7.92 (d, 1H), 7.74 (m,1H) 7.64 (d, 2H), 7.53 (m, 1H), 7.34 (d, 2H), 2.62 (s, 2H), 1.66 (m,1H), 0.43 (m, 2H), 0.20 ppm (m, 2H)

LCMS: MH⁺=304.1

Compound 62:

NMR (300 MHz, CDCl₃): 8.34 (s, 1H), 8.21 (m, 1H), 7.94 (d, 1H), 7.74 (m,1H) 7.65 (d, 2H), 7.53 (m, 1H), 7.35 (d, 2H), 2.67 (s, 2H), 1.69 (m,2H), 0.40 (m, 3H), 0.15 ppm (m, 2H)

LCMS: MH⁺=318.1

Compound 63:

NMR (300 MHz, CDCl₃): 8.36 (s, 1H), 8.23 (m, 1H), 7.96 (d, 1H), 7.76 (m,1H) 7.64 (d, 2H), 7.56 (m, 1H), 7.34 (d, 2H), 2.68 (s, 2H), 1.22 (d,2H), 1.02 (s, 6H), 0.40 (m, 3H), 0.15 ppm (m, 2H)

LCMS: MH⁺=360.1

Compound 64:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H), 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.53 (s,2H), 1.79 (m, 2H), 1.51 (m, 2H), 0.99 (m, 3H), 0.98 ppm (s, 9H)

LCMS: MH⁺=351.2

Compound 65:

NMR (400 MHz, CDCl₃): 7.93 (d, 1H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H), 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.53 (s,2H), 2.46 (s, 3H), 1.79 (m, 2H), 1.51 (m, 2H), 0.99 (m, 3H), 0.98 ppm(s, 9H)

LCMS: MH⁺=365.2

Compound 66:

NMR (400 MHz, CDCl₃): 7.93 (d, 1H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H), 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.60 (m,2H), 2.53 (s, 2H), 1.79 (m, 2H), 1.51 (m, 2H), 1.25 (m, 3H), 0.99 (m,3H), 0.98 ppm (s, 9H)

LCMS: MH⁺=379.2

Compound 67:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.52 (m,1H), 7.44 (m, 1H), 7.35 (m, 1H), 7.13 (m, 1H), 7.00 (d, 1H), 4.36 (m,2H), 2.53 (s, 2H), 2.48 (s, 3H), 1.79 (m, 2H), 1.51 (m, 2H), 0.99 (m,3H), 0.98 ppm (s, 9H)

LCMS: MH⁺=365.2

Compound 68:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.52 (m,1H), 7.44 (m, 1H), 7.35 (m, 1H), 7.13 (m, 1H), 7.00 (d, 1H), 4.36 (m,2H), 2.60 (m, 2H), 2.53 (s, 2H), 1.79 (m, 2H), 1.51 (m, 2H), 1.25 (m,3H), 0.99 (m, 3H), 0.98 ppm (s, 9H)

LCMS: MH⁺=379.2

Compound 69:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.53 (s, 2H), 2.34 (s,3H), 1.79 (m, 2H), 1.51 (m, 2H), 0.99 (m, 3H), 0.98 ppm (s, 9H)

LCMS: MH⁺=365.2

Compound 70:

NMR (400 MHz, CDCl₃): 7.92 (m, 1H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.53 (s, 2H), 2.34 (s,3H), 2.22 (s, 3H), 1.79 (m, 2H), 1.51 (m, 2H), 0.99 (m, 3H), 0.98 ppm(s, 9H)

LCMS: MH⁺=379.2

Compound 71:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H), 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.53 (s,2H), 1.85 (m, 2H), 1.05 (m, 3H), 0.94 ppm (s, 9H)

LCMS: MH⁺=337.2

Compound 72:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H), 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.53 (s,2H), 1.79 (m, 2H), 1.43 (m, 4H), 0.99 (s, 9H), 0.97 ppm (m, 3H)

LCMS: MH⁺=351.2

Compound 73:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H), 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 5.33 (m, 1H), 2.54 (s,2H), 1.42 (d, 6H), 0.96 ppm (s, 9H)

LCMS: MH⁺=337.2

Compound 74:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H), 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.03 (m, 2H), 2.41 (s,2H), 2.03 (m, 1H), 1.53 (m, 4H), 1.48 (m, 2H), 1.43 (m, 2H), 1.27 (m,2H), 0.94 ppm (s, 9H)

LCMS: MH⁺=391.2

Compound 75:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H), 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H4.46 (m, 1H), 4.21 (m, 1H),3.33 (m, 1H), 2.79 (m, 1H), 2.69 (m, 1H), 2.41 (s, 2H), 1.55 (m, 1H),1.48 (m, 2H), 1.45 (m, 1H), 0.94 ppm (s, 9H)

LCMS: MH⁺=392.2

Compound 76:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.47 (m,4H), 7.38 (m, 4H), 7.13 (d, 2H), 7.00 (d, 1H), 5.26 (m, 2H), 2.53 (s,2H), 0.98 ppm (s, 9H)

LCMS: MH⁺=385.2

Compound 77:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H), 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 3.91 (m, 1H), 2.53 (s,2H), 1.99 (m, 2H), 1.74 (m, 2H), 1.53 (m, 2H), 1.48 (m, 2H), 1.43 (m,2H), 0.94 ppm (s, 9H)

LCMS: MH⁺=377.2

Compound 78:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H), 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.63 (m,1H), 2.38 (m, 1H), 2.04 (m, 1H), 1.80 (m, 2H), 1.55 (m, 2H), 1.45 (m,2H), 0.96 (m, 3H), 0.90 ppm (m, 6H)

LCMS: MH⁺=351.2

Compound 79:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H), 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.54 (m,2H), 1.89 (m, 1H), 1.80 (m, 2H), 1.60 (m, 2H), 1.56 (m, 2H), 1.46 (m,4H), 1.35 (m, 2H), 0.90 ppm (m, 3H)

LCMS: MH⁺=363.2

Compound 80:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H), 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.29 (m, 2H), 1.81 (m,1H), 1.53 (m, 4H), 1.48 (m, 2H), 1.44 (m, 2H), 1.27 (m, 2H), 0.90 ppm(m, 3H)

LCMS: MH⁺=377.2

Compound 81:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H), 7.35 (m, 3H), 7.23 (m, 3H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m,2H), 1.79 (m, 2H), 1.51 (m, 2H), 0.90 ppm (m, 3H)

LCMS: MH⁺=371.2

Compound 82:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.59 (m, 1H), 7.48 (d, 2H), 7.35 (m,1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.42 (m, 5H), 1.80 (m,2H), 1.45 (m, 2H), 0.94 (s, 9H), 0.90 ppm (m, 3H)

LCMS: MH⁺=365.2

Compound 83:

NMR (400 MHz, CDCl₃): 7.92 (m, 1H), 7.59 (m, 1H), 7.48 (d, 2H), 7.35 (m,1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.48 (s, 3H), 2.42 (m,5H), 1.80 (m, 2H), 1.45 (m, 2H), 0.94 (s, 9H), 0.90 ppm (m, 3H)

LCMS: MH⁺=379.2

Compound 84:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.59 (m, 1H), 7.50 (m, 1H), 7.46 (m,1H), 7.35 (m, 1H), 7.13 (m, 1H), 7.00 (d, 1H), 4.36 (m, 2H), 2.48 (s,3H), 2.42 (m, 5H), 1.80 (m, 2H), 1.45 (m, 2H), 0.94 (s, 9H), 0.90 ppm(m, 3H)

LCMS: MH⁺=379.2

Compound 85:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.59 (m, 1H), 7.48 (d, 2H), 7.13 (d,2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.42 (m, 5H), 2.34 (s, 3H), 1.80 (m,2H), 1.45 (m, 2H), 0.94 (s, 9H), 0.90 ppm (m, 3H)

LCMS: MH⁺=379.2

Compound 86:

NMR (400 MHz, CDCl₃): 7.92 (m, 1H), 7.59 (m, 1H), 7.48 (d, 2H), 7.13 (d,2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.42 (m, 5H), 2.34 (s, 3H), 2.22 (s,3H), 1.80 (m, 2H), 1.45 (m, 2H), 0.94 (s, 9H), 0.90 ppm (m, 3H)

LCMS: MH⁺=393.2

Compound 87:

NMR (400 MHz, CDCl₃): 77.94 (m, 2H), 7.59 (m, 1H), 7.48 (d, 2H), 7.35(m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.42 (m, 5H), 1.91(m, 2H), 0.94 (s, 9H), 0.90 ppm (m, 3H)

LCMS: MH⁺=351.2

Compound 88:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.59 (m, 1H), 7.48 (d, 2H), 7.35 (m,1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.42 (m, 5H), 1.80 (m,2H), 1.39 (m, 2H), 1.31 (m, 2H), 0.94 (s, 9H), 0.90 ppm (m, 3H)

LCMS: MH⁺=379.2

Compound 89:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.59 (m, 1H), 7.48 (d, 2H), 7.35 (m,1H), 7.13 (d, 2H), 7.00 (d, 1H), 5.33 (m, 1H), 2.54 (s, 2H), 2.42 (m,3H), 1.42 (d, 6H), 0.96 ppm (s, 9H)

LCMS: MH⁺=351.2

Compound 90:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.59 (m, 1H), 7.48 (d, 2H), 7.35 (m,1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.42 (m, 5H), 2.03 (m,1H), 1.53 (m, 4H), 1.43 (m, 2H), 1.27 (m, 2H), 1.48 (m, 2H), 0.94 ppm(s, 9H)

LCMS: MH⁺=405.2

Compound 91:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.59 (m, 1H), 7.48 (d, 2H), 7.35 (m,1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 3.33 (m, 1H), 2.79 (m,1H), 2.69 (m, 1H), 2.42 (m, 5H), 1.55 (m, 1H), 1.48 (m, 2H), 1.45 (m,1H), 0.94 ppm (s, 9H)

LCMS: MH⁺=406.3

Compound 92:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.59 (m, 1H), 7.48 (m, 4H) 7.36 (m,4H), 7.13 (d, 2H), 7.00 (d, 1H), 5.26 (m, 2H), 2.53 (s, 2H), 0.98 ppm(s, 9H)

LCMS: MH⁺=399.2

Compound 93:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.59 (m, 1H), 7.48 (d, 2H), 7.35 (m,1H), 7.13 (d, 2H), 7.00 (d, 1H), 3.91 (m, 1H), 2.42 (s, 2H), 1.99 (m,2H), 1.74 (m, 2H), 1.53 (m, 2H), 1.48 (m, 2H), 1.43 (m, 2H), 0.94 ppm(s, 9H)

LCMS: MH⁺=391.3

Compound 94:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.59 (m, 1H), 7.48 (d, 2H), 7.35 (m,1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.63 (m, 1H), 2.42 (m,3H), 2.38 (m, 1H), 2.04 (m, 1H), 1.80 (m, 2H), 1.55 (m, 2H), 1.45 (m,2H), 0.96 (m, 3H), 0.90 ppm (m, 6H)

LCMS: MH⁺=365.2

Compound 95:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.59 (m, 1H), 7.48 (d, 2H), 7.35 (m,1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.54 (m, 2H), 2.42 (m,3H), 1.89 (m, 1H), 1.80 (m, 2H), 1.60 (m, 2H), 1.56 (m, 2H), 1.46 (m,4H), 1.35 (m, 2H), 0.90 ppm (m, 3H)

LCMS: MH⁺=377.2

Compound 96:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.59 (m, 1H), 7.48 (d, 2H), 7.35 (m,1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.42 (m, 3H), 1.81 (m,3H), 1.53 (m, 4H), 1.48 (m, 2H), 1.44 (m, 4H), 0.90 ppm (m, 3H)

LCMS: MH⁺=391.2

Compound 97:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.59 (m, 1H), 7.48 (d, 2H), 7.35 (m,1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.53 (s, 2H), 2.48 (s,3H), 1.79 (m, 2H), 1.51 (m, 2H), 0.92 ppm (m, 3H)

LCMS: MH⁺=385.2

Compound 98:

NMR (400 MHz, CDCl₃): 7.98 (m, 2H), 7.63 (m, 1H), 7.49 (d, 2H), 7.36 (m,1H), 7.17 (d, 2H), 6.84 (m, 1H), 4.36 (m, 2H), 2.53 (s, 2H), 2.02 (s,2H), 1.79 (m, 2H), 1.51 (m, 2H), 0.99 (m, 3H), 0.98 ppm (s, 9H)

LCMS: MH⁺=366.2

Compound 99:

NMR (400 MHz, CDCl₃): 7.94 (m, 1H), 7.63 (m, 1H), 7.49 (d, 2H), 7.36 (m,1H), 7.17 (d, 2H), 6.84 (m, 1H), 4.36 (m, 2H), 2.53 (s, 2H), 2.48 (s,3H), 2.02 (s, 2H), 1.79 (m, 2H), 1.51 (m, 2H), 0.99 (m, 3H), 0.98 ppm(s, 9H)

LCMS: MH⁺=380.2

Compound 100:

NMR (400 MHz, CDCl₃): 7.98 (m, 2H), 7.63 (m, 1H), 7.48 (m, 1H), 7.36 (m,1H), 7.17 (m, 1H), 6.84 (m, 1H), 4.36 (m, 2H), 2.53 (s, 2H), 2.48 (s,3H), 2.02 (s, 2H), 1.79 (m, 2H), 1.51 (m, 2H), 0.99 (m, 3H), 0.98 ppm(s, 9H)

LCMS: MH⁺=380.3

Compound 101:

NMR (400 MHz, CDCl₃): 7.98 (m, 2H), 7.63 (m, 1H), 7.49 (d, 2H), 7.17 (d,2H), 6.84 (m, 1H), 4.36 (m, 2H), 2.53 (s, 2H), 2.34 (s, 3H), 2.02 (s,2H), 1.79 (m, 2H), 1.51 (m, 2H), 0.99 (m, 3H), 0.98 ppm (s, 9H)

LCMS: MH⁺=380.3

Compound 102:

NMR (400 MHz, CDCl₃): 7.96 (m, 1H), 7.63 (m, 1H), 7.49 (d, 2H), 7.17 (d,2H), 6.84 (m, 1H), 4.36 (m, 2H), 2.53 (s, 2H), 2.34 (s, 3H), 2.22 (s,3H), 2.02 (s, 2H), 1.79 (m, 2H), 1.51 (m, 2H), 0.99 (m, 3H), 0.98 ppm(s, 9H)

LCMS: MH⁺=394.3

Compound 103:

NMR (400 MHz, CDCl₃): 7.98 (m, 2H), 7.63 (m, 1H), 7.49 (d, 2H), 7.36 (m,1H), 7.17 (d, 2H), 6.84 (m, 1H), 4.36 (m, 2H), 2.53 (s, 2H), 2.02 (s,2H), 1.79 (m, 2H), 1.50 (m, 4H), 0.98 (s, 9H), 0.96 ppm (m, 3H)

LCMS: MH⁺=380.3

Compound 104:

NMR (400 MHz, CDCl₃): 7.98 (m, 2H), 7.63 (m, 1H), 7.49 (d, 2H), 7.36 (m,1H), 7.17 (d, 2H), 6.84 (m, 1H), 5.33 (m, 1H), 2.54 (s, 2H), 2.02 (s,2H), 1.43 (d, 6H), 0.96 ppm (s, 9H)

LCMS: MH⁺=352.2

Compound 105:

NMR (400 MHz, CDCl₃): 7.98 (m, 2H), 7.63 (m, 1H), 7.49 (d, 2H), 7.36 (m,1H), 7.17 (d, 2H), 6.84 (m, 1H), 4.03 (m, 2H), 2.53 (s, 2H), 2.02 (m,3H), 1.52 (m, 4H), 1.48 (m, 2H), 1.43 (m, 2H), 1.27 ppm (m, 2H)

LCMS: MH⁺=406.3

Compound 106:

NMR (400 MHz, CDCl₃): 7.98 (m, 2H), 7.63 (m, 1H), 7.49 (m, 4H), 7.36 (m,4H), 7.17 (d, 2H), 6.84 (m, 1H), 5.26 (m, 2H), 2.53 (s, 2H), 2.02 (s,2H), 0.98 ppm (s, 9H)

LCMS: MH⁺=400.2

Compound 107:

NMR (400 MHz, CDCl₃): 7.98 (m, 2H), 7.63 (m, 1H), 7.49 (d, 2H), 7.36 (m,1H), 7.17 (d, 2H), 6.84 (m, 1H), 3.91 (m, 1H), 2.53 (s, 2H), 2.02 (s,2H), 1.99 (m, 2H), 1.74 (m, 2H), 1.53 (m, 2H), 1.48 (m, 2H), 1.43 (m,1H), 0.98 ppm (s, 9H)

LCMS: MH⁺=392.3

Compound 108:

NMR (400 MHz, CDCl₃): 7.98 (m, 2H), 7.63 (m, 1H), 7.49 (d, 2H), 7.36 (m,1H), 7.17 (d, 2H), 6.84 (m, 1H), 4.36 (m, 2H), 2.63 (m, 1H), 2.38 (m,1H), 2.02 (m, 3H), 1.79 (m, 2H), 1.55 (m, 2H), 1.51 (m, 2H), 0.96 (m,3H), 0.92 ppm (m, 6H)

LCMS: MH⁺=366.2

Compound 109:

NMR (400 MHz, CDCl₃): 7.98 (m, 2H), 7.63 (m, 1H), 7.49 (d, 2H), 7.36 (m,1H), 7.17 (d, 2H), 6.84 (m, 1H), 4.36 (m, 2H), 2.53 (d, 2H), 2.02 (s,2H), 1.89 (m, 1H), 1.79 (m, 2H), 1.57 (m, 4H), 1.51 (m, 2H), 1.40 (m,4H), 0.99 ppm (m, 3H)

LCMS: MH⁺=378.2

Compound 110:

NMR (400 MHz, CDCl₃): 7.98 (m, 2H), 7.63 (m, 1H), 7.49 (d, 2H), 7.36 (m,1H), 7.17 (d, 2H), 6.84 (m, 1H), 4.36 (m, 2H), 2.53 (d, 2H), 2.02 (s,2H), 1.80 (m, 3H), 1.51 (m, 6H), 1.48 (m, 2H), 1.43 (m, 2H), 0.98 ppm(m, 3H)

LCMS: MH⁺=392.3

Compound 111:

NMR (400 MHz, CDCl₃): 7.98 (m, 2H), 7.63 (m, 1H), 7.49 (d, 2H), 7.36 (m,3H), 7.23 (m, 3H), 7.17 (d, 2H), 6.84 (m, 1H), 4.36 (m, 2H), 3.96 (s,2H), 2.02 (s, 2H), 1.79 (m, 2H), 1.51 (m, 2H), 0.98 ppm (m, 3H)

LCMS: MH⁺=386.2

Compound 112:

NMR (400 MHz, CDCl₃): 7.97 (m, 2H), 7.62 (m, 1H), 7.48 (d, 2H), 7.36 (m,1H), 7.17 (d, 2H), 6.90 (m, 1H), 4.36 (m, 2H), 2.53 (s, 2H), 1.79 (m,2H), 1.51 (m, 2H), 0.99 (m, 3H), 0.98 ppm (s, 9H)

LCMS: MH⁺=369.2

Compound 113:

NMR (400 MHz, CDCl₃): 7.92 (m, 1H), 7.59 (m, 1H), 7.48 (d, 2H), 7.35 (m,1H), 7.13 (d, 2H), 7.00 (m, 1H), 4.36 (m, 2H), 2.53 (s, 2H), 2.48 (s,3H), 1.79 (m, 2H), 1.51 (m, 2H), 0.99 (m, 3H), 0.98 ppm (s, 9H)

LCMS: MH⁺=399.2

Compound 114:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.59 (m, 1H), 7.50 (m, 1H), 7.46 (m,1H), 7.35 (m, 1H), 7.13 (m, 1H), 7.00 (d, 1H), 4.36 (m, 2H), 2.53 (s,2H), 2.48 (s, 3H), 1.79 (m, 2H), 1.51 (m, 2H), 0.99 (m, 3H), 0.98 ppm(s, 9H)

LCMS: MH⁺=443.2

Compound 115:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.59 (m, 1H), 7.48 (d, 2H), 7.13 (d,2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.53 (s, 2H), 2.34 (s, 3H), 1.79 (m,2H), 1.51 (m, 2H), 0.99 (m, 3H), 0.98 ppm (s, 9H)

LCMS: MH⁺=491.1

Compound 116:

NMR (400 MHz, CDCl₃): 7.94 (m, 1H), 7.62 (m, 1H), 7.48 (d, 2H), 7.17 (d,2H), 6.90 (m, 1H), 4.36 (m, 2H), 2.53 (s, 2H), 2.34 (s, 3H), 2.22 (s,3H), 1.79 (m, 2H), 1.51 (m, 2H), 0.99 (m, 3H), 0.98 ppm (s, 9H)

LCMS: MH⁺=397.3

Compound 117:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.59 (m, 1H), 7.48 (d, 2H), 7.35 (m,1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.54 (s, 2H), 1.79 (m,2H), 1.48 (m, 4H), 0.98 (s, 9H), 0.96 ppm (m, 3H)

LCMS: MH⁺=399.2

Compound 118:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.59 (m, 1H), 7.48 (d, 2H), 7.35 (m,1H), 7.13 (d, 2H), 7.00 (d, 1H), 5.33 (m, 1H), 2.53 (s, 2H), 1.42 (d,6H), 0.96 ppm (s, 9H)

LCMS: MH⁺=415.1

Compound 119:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.59 (m, 1H), 7.48 (d, 2H), 7.35 (m,1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.03 (m, 2H), 2.41 (s, 2H), 2.03 (m,1H), 1.53 (m, 4H), 1.48 (m, 2H), 1.43 (m, 2H), 1.27 (m, 2H), 0.94 ppm(s, 9H)

LCMS: MH⁺=517.2

Compound 120:

NMR (400 MHz, CDCl₃): 7.97 (m, 2H), 7.62 (m, 1H), 7.47 (m, 4H), 7.37 (m,4H), 7.17 (d, 2H), 6.90 (m, 1H), 5.26 (m, 2H), 2.42 (s, 2H), 0.94 ppm(s, 9H)

LCMS: MH⁺=403.2

Compound 121:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.59 (m, 1H), 7.48 (d, 2H), 7.35 (m,1H), 7.13 (d, 2H), 7.00 (d, 1H), 3.91 (m, 1H), 2.53 (s, 2H), 1.99 (m,2H), 1.74 (m, 2H), 1.49 (m, 4H), 1.43 (m, 3H), 0.96 ppm (s, 9H)

LCMS: MH⁺=411.2

Compound 122:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.59 (m, 1H), 7.48 (d, 2H), 7.35 (m,1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.63 (m, 1H), 2.38 (m,1H), 1.79 (m, 2H), 1.51 (m, 2H), 0.99 (m, 3H), 0.96 ppm (m, 6H)

LCMS: MH⁺=429.1

Compound 123:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.59 (m, 1H), 7.48 (d, 2H), 7.34 (m,3H), 7.24 (m, 3H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 3.96 (s,2H), 1.79 (m, 2H), 1.51 (m, 2H), 0.98 ppm (m, 3H)

LCMS: MH⁺=497.1

Compound 124:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H) 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 3.96 (s, 3H), 2.53 (s,2H), 0.94 ppm (m, 9H)

LCMS: MH⁺=309.2

Compound 125:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H) 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 3.95 (s, 3H), 2.63 (m,1H), 2.38 (m, 1H), 1.65 (m, 1H), 1.21 (m, 2H), 0.94 (m, 3H), 0.87 ppm(d, 3H)

LCMS: MH⁺=309.2

Compound 126:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H) 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 3.95 (s, 3H), 2.63 (m,2H), 2.11 (m, 1H), 1.65 ppm (m, 6H)

LCMS: MH⁺=321.2

Compound 127:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H) 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 3.92 (s, 3H), 2.48 (d,2H), 2.14 (m, 1H), 1.24 ppm (m, 10H)

LCMS: MH⁺=335.2

Compound 128:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H) 7.34 (m, 3H), 7.25 (m, 3H), 7.13 (d, 2H), 7.00 (d, 1H), 3.92 (s,3H), 3.89 ppm (s, 2H)

LCMS: MH⁺=329.2

Compound 129:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H) 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 3.93 (s, 3H), 2.48 (d,2H), 1.88 (m, 1H), 0.91 ppm (d, 6H)

LCMS: MH⁺=295.2

Compound 130:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H) 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 3.92 (s, 3H), 2.60 (m,2H), 1.62 (m, 2H), 1.33 (m, 4H), 0.90 ppm (m, 3H)

LCMS: MH⁺=309.2

Compound 131:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H) 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.35 (m, 2H), 2.49 (d,2H), 1.91 (m, 1H), 1.78 (m, 2H), 1.50 (m, 2H), 0.95 (m, 3H), 0.91 ppm(d, 6H)

LCMS: MH⁺=337.2

Compound 132:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H) 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.37 (m, 2H), 2.64 (m,2H), 1.85 (m, 2H), 1.68 (m, 2H), 1.53 (m, 2H), 1.37 (m, 4H), 098 (m,3H), 0.92 ppm (m, 3H)

LCMS: MH⁺=351.2

Compound 133:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H), 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 2.53 (s, 2H), 3.27 (m,4H), 1.92 (m, 4H), 0.96 ppm (s, 9H)

LCMS: MH⁺=364.2

Compound 134:

NMR (400 MHz, CDCl₃): 8.11 (m, 2H), 7.78 (d, 1H), 7.65 (m, 1H), 7.52 (d,2H), 7.37 (m, 1H), 7.17 (d, 2H), 7.06 (d, 1H), 2.54 (s, 2H), 0.96 ppm(s, 9H)

LCMS: MH⁺=295.2

Compound 135:

NMR (400 MHz, CDCl₃): 8.07 (d, 1H), 7.78 (d, 1H), 7.59 (m, 1H), 7.52 (d,2H), 7.17 (d, 2H), 7.06 (d, 1H), 6.84 (m, 1H), 2.54 (s, 2H), 0.96 ppm(s, 9H)

LCMS: MH⁺=311.2

Compound 136:

NMR (400 MHz, CDCl₃): 8.09 (m, 2H), 7.78 (d, 1H), 7.52 (d, 2H), 7.17 (d,2H), 7.07 (m, 2H), 2.54 (s, 2H), 0.96 ppm (s, 9H)

LCMS: MH⁺=311.2

Compound 137:

NMR (400 MHz, CDCl₃): 8.07 (d, 1H), 7.78 (d, 1H), 7.60 (m, 1H), 7.52 (d,2H), 7.17 (d, 2H), 7.13 (m, 1H), 7.06 (d, 1H), 6.55 (s, 2H), 2.54 (s,2H), 0.96 ppm (s, 9H)

LCMS: MH⁺=310.2

Compound 138:

NMR (400 MHz, CDCl₃): 8.06 (m, 2H), 7.78 (d, 1H), 7.52 (d, 2H), 7.41 (m,1H), 7.17 (d, 2H), 7.06 (d, 1H), 6.55 (s, 2H), 2.54 (s, 2H), 0.96 ppm(s, 9H)

LCMS: MH⁺=310.2

Compound 139:

NMR (400 MHz, CDCl₃): 8.07 (d, 1H), 7.78 (d, 1H), 7.59 (m, 1H), 7.52 (d,2H), 7.21 (m, 1H), 7.17 (d, 2H), 7.06 (d, 1H), 2.54 (s, 2H), 2.48 (s,3H), 0.96 ppm (s, 9H)

LCMS: MH⁺=309.2

Compound 140:

NMR (400 MHz, CDCl₃): 8.04 (m, 2H), 7.78 (d, 1H), 7.55 (m, 1H), 7.52 (d,2H), 7.17 (d, 2H), 7.06 (d, 1H), 2.54 (s, 2H), 2.34 (s, 3H), 0.96 ppm(s, 9H)

LCMS: MH⁺=309.2

Compound 141:

NMR (400 MHz, CDCl₃): 7.72 (d, 1H), 7.59 (m, 2H), 7.47 (m, 1H), 7.46 (d,2H), 7.32 (m, 1H), 7.13 (d, 2H), 7.07 (d, 1H), 6.60 (s, 1H), 6.10 (s,1H), 2.53 (s, 2H), 0.95 ppm (s, 9H)

LCMS: MH⁺=294.2

Compound 142:

NMR (400 MHz, CDCl₃): 8.34 (s, 1H), 8.17 (m, 1H), 8.04 (m, 2H), 7.74 (m,3H), 7.48 (d, 2H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.53 (s,2H), 1.79 (m, 2H), 1.51 (m, 2H), 0.99 (m, 3H), 0.98 ppm (s, 9H)

LCMS: MH⁺=401.2

Compound 143:

NMR (400 MHz, CDCl₃): 8.37 (s, 1H), 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m,1H), 7.48 (m, 1H), 7.35 (m, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.53 (s,2H), 1.79 (m, 2H), 1.51 (m, 2H), 0.99 (m, 3H), 0.98 ppm (s, 9H)

LCMS: MH⁺=352.2

Compound 144:

NMR (400 MHz, CDCl₃): 8.39 (s, 1H), 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m,1H), 7.48 (m, 1H), 7.35 (m, 1H), 7.13 (m, 1H), 7.00 (d, 1H), 4.36 (m,2H), 2.53 (s, 2H), 1.79 (m, 2H), 1.51 (m, 2H), 0.99 (m, 3H), 0.98 ppm(s, 9H)

LCMS: MH⁺=352.2

Compound 145:

NMR (400 MHz, CDCl₃): 8.61 (m, 1H), 7.92 (m, 1H), 7.74 (d, 1H), 7.59 (m,1H), 7.48 (d, 2H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.53 (s,2H), 1.79 (m, 2H), 1.51 (m, 2H), 0.99 (m, 3H), 0.98 ppm (s, 9H)

LCMS: MH⁺=352.2

Compound 146:

NMR (400 MHz, CDCl₃): 9.17 (s, 1H), 8.27 (m, 1H), 7.94 (m, 1H), 7.74 (d,1H), 7.48 (d, 2H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.53 (s,2H), 1.79 (m, 2H), 1.51 (m, 2H), 0.99 (m, 3H), 0.98 ppm (s, 9H)

LCMS: MH⁺=352.2

Compound 147:

NMR (400 MHz, CDCl₃): 8.90 (s, 1H), 8.00 (m, 1H), 7.94 (d, 1H), 7.74 (d,1H), 7.48 (d, 2H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.53 (s,2H), 1.79 (m, 2H), 1.51 (m, 2H), 0.99 (m, 3H), 0.98 ppm (s, 9H)

LCMS: MH⁺=352.2

Compound 148:

NMR (400 MHz, CDCl₃): 8.76 (m, 1H), 7.94 (m, 1H), 7.74 (d, 1H), 7.48 (d,2H), 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 2H), 2.53 (s,2H), 1.79 (m, 2H), 1.51 (m, 2H), 0.99 (m, 3H), 0.98 ppm (s, 9H)

LCMS: MH⁺=352.2

Compound 149:

NMR (400 MHz, CDCl₃): 7.94 (m, 2H), 7.74 (d, 1H), 7.59 (m, 1H), 7.48 (d,2H), 7.35 (m, 1H), 7.13 (d, 2H), 7.00 (d, 1H), 4.36 (m, 4H), 2.53 (s,2H), 1.79 (m, 4H), 1.51 (m, 4H), 0.99 (m, 6H), 0.98 ppm (s, 9H)

LCMS: MH⁺=451.3

Compound 150:

NMR (400 MHz, CDCl₃): 8.15 (d, 1H), 7.78 (d, 1H), 7.52 (d, 2H), 7.31 (m,1H), 7.17 (d, 2H), 7.06 (d, 1H), 7.12 (m, 1H), 2.54 (s, 2H), 0.96 ppm(s, 9H)

LCMS: MH⁺=311.2

Compound 151:

NMR (400 MHz, CDCl₃): 8.15 (d, 1H), 7.78 (d, 1H), 7.52 (d, 2H), 7.41 (m,1H), 7.32 (m, 1H), 7.17 (d, 2H), 7.06 (d, 1H), 6.55 (s, 2H), 2.54 (s,2H), 0.96 ppm (s, 9H)

LCMS: MH⁺=310.2

Compound 152:

NMR (400 MHz, CDCl₃): 8.15 (d, 1H), 7.78 (d, 1H), 7.52 (d, 2H), 7.49 (m,1H), 7.29 (m, 1H), 7.17 (d, 2H), 7.06 (d, 1H), 2.54 (s, 2H), 2.48 (s,3H), 0.96 ppm (s, 9H)

LCMS: MH⁺=309.2

Compound 153:

NMR (400 MHz, CDCl₃): 8.09 (m, 2H), 7.78 (d, 1H), 7.52 (d, 2H), 7.17 (d,2H), 7.06 (d, 1H), 6.81 (m, 1H), 2.54 (s, 2H), 0.96 ppm (s, 9H)

LCMS: MH⁺=311.2

Compound 154:

NMR (400 MHz, CDCl₃): 8.10 (m, 2H), 7.78 (d, 1H), 7.52 (d, 2H), 7.17 (d,2H), 7.14 (m, 1H), 7.06 (d, 1H), 6.55 (s, 2H), 2.54 (s, 2H), 0.96 ppm(s, 9H)

LCMS: MH⁺=310.2

Compound 155:

NMR (400 MHz, CDCl₃): 8.10 (m, 2H), 7.78 (d, 1H), 7.52 (d, 2H), 7.21 (m,1H), 7.17 (d, 2H), 7.06 (d, 1H), 2.54 (s, 2H), 2.34 (s, 3H), 0.96 ppm(s, 9H)

LCMS: MH⁺=309.2

INDUSTRIAL APPLICABILITY

The novel stilbene derivatives of the present invention can be used asan inhibitor of the function of cyclophilin, which has an improvedpharmaceutical profile.

What is claimed is:
 1. A method of inhibiting activities of cyclophilinin a subject, the method comprising: administering, to a subject in needof such inhibition, an effective amount of a composition comprising acompound of Chemical Formula 1 or a pharmaceutically acceptable saltthereof:

in Chemical Formula 1, A is CRa or N, B is CRb or N, G is CRe or N, J isCRf or N, M is CRg or N, D, E, and L are CRh or N, Rx is H, CH₃, CN,NH₂, F, Cl, Br or I, wherein when Rx is H, CH₃, NH₂, F, Cl, Br or I, Rais hydrogen, NO₂, CN, OH, a C1-C5 alkyl group, a C2-C10 alkenyl group, aC1-C2 alkoxy group, —COOR1 (R1 is hydrogen or a C1-C5 alkyl group) or—OCOR2 (R2 is a C1-C5 alkyl group), Rb is hydrogen, a C1-C20 alkylgroup, a C2-C10 alkenyl group, a C1-C10 alkoxy group, —COOR1 (R1 ishydrogen or a C1-C5 alkyl group) or —OCOR2 (R2 is a C1-C5 alkyl group),Rc is NO₂, a C1-C20 alkyl group, a C3-C10 cycloalkyl group, a C3-C10alkoxy group, a C6-C12 aryl, a C5-C12 heterocyclic group, —NR3R4 (R3 ishydrogen, a C1-C20 alkyl group or a C6-C12 aryl, R4 is hydrogen, aC1-C20 alkyl group or a C6-C12 aryl, and R3 and R4 are linked to form aheterocycle, further containing at least one hetero atom), —COOR5 (R5 isa C1-C20 alkyl group, a C6-C12 aryl or a C3-C10 cycloalkyl group),—NR7CYR8 (Y is O or S, R7 is hydrogen or a C1-C5 alkyl group, and R8 isa C1-C20 alkyl group, a C6-C12 aryl, a C3-C10 cycloalkyl group or aC5-C12 heterocyclic group), —NHS(O)₂R9 (R9 is a C6-C12 aryl or a C5-C12heterocyclic group), or —COR10 (R10 is a C1-C20 alkyl group, a C6-C12aryl, a C3-C10 cycloalkyl group or a C5-C12 heterocyclic group), Rd ishalogen, NO₂, COOH, CN, a C2-C20 alkyl group, a C3-C10 cycloalkyl group,a C1-C10 alkoxy group, a C6-C12 aryl, a C5-C12 heterocyclic group,—NR3R4 (R3 is hydrogen, a C1-C20 alkyl or a C6-C12 aryl, R4 is hydrogen,a C1-C20 alkyl or a C6-C12 aryl, and R3 and R4 are linked to form aheterocycle, further containing at least one hetero atom), —COOR5 (R5 isa C1-C20 alkyl group, a C6-C12 aryl or a C3-C10 cycloalkyl group),—OCOR6 (R6 is a C1-C20 alkyl group, a C6-C12 aryl or a C3-C10 cycloalkylgroup), —NR7CYR8 (Y is O or S, R7 is hydrogen or a C1-C5 alkyl group,and R8 is a C1-C20 alkyl group, a C6-C12 aryl, a C3-C10 cycloalkyl groupor a C5-C12 heterocyclic group), —NHS(O)₂R9 (R9 is a C6-C12 aryl or aC5-C12 heterocyclic group), or COR10 (R10 is a C1-C20 alkyl group, aC6-C12 aryl, a C3-C10 cycloalkyl group or a C5-C12 heterocyclic group),Re is hydrogen, NH₂, OH, CN, a C1-C20 alkyl group, a C2-C10 alkenylgroup, a C1-C10 alkoxy, a C6-C12 aryl, a C5-C12 heterocyclic group,—NR7CYR8 (Y is O or S, R7 is hydrogen or a C1-C5 alkyl group, and R8 isa C1-C20 alkyl group, a C6-C12 aryl, a C3-C10 cycloalkyl group or aC5-C12 heterocyclic group) or —NHS(O)₂R9 (R9 is a C6-C12 aryl or aC5-C12 heterocyclic group), Rf is hydrogen, NH₂, OH, NO₂, a C1-C4 alkylgroup, a C2-C10 alkenyl group, a C1-C4 alkoxy group, a C6-C12 aryl, aC5-C12 heterocyclic group, —NHR11 (R11 is a C1-C2 alkyl group), —COOR12(R12 is a C1-C2 alkyl group), —OCOR13 (R13 is a C1-C2 alkyl group), or—COR14 (R14 is a C1-C2 alkyl group), Rg is hydrogen, NH₂, OH, halogen,NO₂, COOH, CN, a C1-C20 alkyl group, a C2-C10 alkenyl group, a C3-C10cycloalkyl group, a C1-C10 alkoxy group, a C6-C12 aryl, a C5-C12heterocyclic group, —NR3R4 (R3 is hydrogen, a C1-C20 alkyl or a C6-C12aryl, R4 is hydrogen, a C1-C20 alkyl or a C6-C12 aryl, and R3 and R4 arelinked to form a heterocycle, further containing at least one heteroatom), —COOR5 (R5 is a C1-C20 alkyl group, a C6-C12 aryl or a C3-C10cycloalkyl group), —OCOR6 (R6 is a C1-C20 alkyl group, a C6-C12 aryl ora C3-C10 cycloalkyl group), —NR7CYR8 (Y is O or S, R7 is hydrogen or aC1-C5 alkyl group, and R8 is a C1-C20 alkyl group, a C6-C12 aryl, aC3-C10 cycloalkyl group or a C5-C12 heterocyclic group), —NHS(O)₂R9 (R9is a C6-C12 aryl or a C5-C12 heterocyclic group), or —COR10 (R10 is aC1-C20 alkyl group, a C6-C12 aryl, a C3-C10 cycloalkyl group or a C5-C12heterocyclic group), and Rh is hydrogen, NH₂, OH, a C1-C5 alkyl group ora C2-C10 alkenyl group, wherein when Rx is CN, Ra is hydrogen, Rb ishydrogen, a C1-C20 alkyl group, a C2-C10 alkenyl group, a C1-C10 alkoxygroup, —COOR1 (R1 is hydrogen or a C1-C5 alkyl group) or —OCOR2 (R2 is aC1-C5 alkyl group), Rc is OH, NO₂, a C1-C20 alkyl group, a C3-C10cycloalkyl group, a C2-C10 alkoxy group, a C6-C12 aryl, a C5-C12heterocyclic group, —NR3R4 (R3 is hydrogen, a C1-C20 alkyl group or aC6-C12 aryl, R4 is hydrogen, a C1-C20 alkyl group or a C6-C12 aryl, andR3 and R4 are linked to form a heterocycle, further containing at leastone hetero atom), —COOR5 (R5 is a C1-C20 alkyl group, a C6-C12 aryl or aC3-C10 cycloalkyl group), —OCOR6 (R6 is a C1-C20 alkyl group, a C6-C12aryl or a C3-C10 cycloalkyl group), —NR7CYR8 (Y is O or S, R7 ishydrogen or a C1-C5 alkyl group, and R8 is a C1-C20 alkyl group, aC6-C12 aryl, a C3-C10 cycloalkyl group or a C5-C12 heterocyclic group),—NHS(O)₂R9 (R9 is a C6-C12 aryl or a C5-C12 heterocyclic group), or—COR10 (R10 is a C1-C20 alkyl group, a C6-C12 aryl, a C3-C10 cycloalkylgroup, or a C5-C12 heterocyclic group), Rd is hydrogen, halogen, NO₂,COOH, CN, a C2-C20 alkyl group, a C3-C10 cycloalkyl group, a C1-C10alkoxy group, a C6-C12 aryl, a C5-C12 heterocyclic group, —NR3R4 (R3 ishydrogen, a C1-C20 alkyl group or a C6-C12 aryl, R4 is hydrogen, aC1-C20 alkyl group or a C6-C12 aryl, and R3 and R4 are linked to form aheterocycle, further containing at least one hetero atom), —COOR5 (R5 isa C1-C20 alkyl group, a C6-C12 aryl or a C3-C10 cycloalkyl group),—OCOR6 (R6 is a C1-C20 alkyl group, a C6-C12 aryl or a C3-C10 cycloalkylgroup), —NR7CYR8 (Y is O or S, R7 is hydrogen or a C1-C5 alkyl group,and R8 is a C1-C20 alkyl group, a C6-C12 aryl, a C3-C10 cycloalkyl groupor a C5-C12 heterocyclic group), —NHS(O)₂R9 (R9 is a C6-C12 aryl or aC5-C12 heterocyclic group), or COR10 (R10 is a C1-C20 alkyl group, aC6-C12 aryl, a C3-C10 cycloalkyl group or a C5-C12 heterocyclic group),Re is hydrogen, CN, a C2-C20 alkyl group, a C2-C10 alkenyl group, aC1-C10 alkoxy, a C6-C12 aryl, a C5-C12 heterocyclic group, —NR7CYR8 (Yis O or S, R7 is hydrogen or a C1-C5 alkyl group, and R8 is a C1-C20alkyl group, a C6-C12 aryl, a C3-C10 cycloalkyl group or a C5-C12heterocyclic group) or —NHS(O)₂R9 (R9 is a C6-C12 aryl or a C5-C12heterocyclic group), Rf and Rg are each hydrogen, and Rh is hydrogen, aC1-C5 alkyl group or a C2-C10 alkenyl group, wherein a hetero atom ofthe heterocyclic group is at least one selected from the groupconsisting of nitrogen, oxygen and sulfur, wherein the alkyl group maybe substituted with at least one substituent selected from the groupconsisting of OH, amine, a C6-C12 aryl, a C5-C10 heterocyclic group anda C3-C10 cycloalkyl group, wherein the alkoxy group may be substitutedwith at least one substituent selected from the group consisting ofhalogen, a C6-C12 aryl, a C3-C10 cycloalkyl group, amine and anaminocarbonyl group, wherein the heterocyclic group may be substitutedwith at least one substituent selected from the group consisting of analkyl group, an amine-substituted alkyl group, amine, an amide group anda carboxyl group, wherein the aryl may be substituted with at least onesubstituent selected from the group consisting of halogen, an alkylgroup, a hydroxyl group, an alkoxy group, a carboxyl group, an estergroup, a nitro group and an amine group, wherein A, B, D, E, G, J, L andM may be linked with an adjacent group to form a fused ring, and whereinRd is not NO₂ when Rb is CH₃.
 2. The method of claim 1, wherein A is CRaor N; B is CRb; G is CRe; J is CRf; M is CRg or N; D is CH; E is CH; andL is CH.
 3. The method of claim 1, wherein Rb is hydrogen or a C1-C8alkyl group.
 4. The method of claim 1, wherein Rc is a C1-C20 alkylgroup, a C3-C10 alkoxy group, a phenylalkyl group, a nitro group, aC3-C10 cycloalkyl group, a C5-C12 heterocyclic group or a C1-C10alkylketone.
 5. The method of claim 1, wherein Rd is a C2-C20 alkylgroup; a C3-C10 ester group; a C3-C10 cycloalkyl group; acycloalkyl-group-substituted methoxy; an amine-group-substituted ethoxy;a carboxyl group; a phenyl-group-substituted C2-C20 alkyl group, thephenyl group being unsubstituted or substituted with a C1-C5 alkylgroup, a C1-C5 alkoxy group, a carboxyl group or an amine group; amine;N-methylpiperazine; piperidine; morpholine; or —COOR5 (R5 is a C1-C20alkyl group, a C6-C12 aryl or a C3-C10 cycloalkyl group).
 6. The methodof claim 1, wherein Re is hydrogen, OH, a C1-C20 alkyl group or a C1-C10alkoxy group.
 7. The method of claim 1, wherein Rg is hydrogen, OH, aC1-C20 alkyl group; a C3-C10 ester group; a C3-C10 cycloalkyl group; acycloalkyl-group-substituted methoxy; an amine-group-substituted ethoxy;a phenyl-group-substituted C2-C20 alkyl group, the phenyl group beingunsubstituted or substituted with a C1-C5 alkyl group, a C1-C5 alkoxygroup, a carboxyl group or an amine group; amine; N-methylpiperazine;piperidine; morpholine; or a carboxyl group.
 8. The method of claim 1,wherein the alkyl group is —CH₃, —CH₂CH₃, —CH₂CH₂CH₃, —CH₂(CH₂)₂CH₃,—CH₂(CH₂)₃CH₃, —CH(CH₃)CH₂CH₃, CH₂CH(CH₃)CH₂CH₃, —CH₂CH₂CH(CH₃)₂,—CH(CH₃)₂, —C(CH₃)₃, —CH₂C(CH₃)₃, —CH₂CH(CH₃)₂, —CH(CH₃)CH(CH₃)₂,—CH(CH₃)C(CH₃)₃, —C(CH₃)₂CH₂CH₃, —C(CH₃)₂CH(CH₃)₂, —C(CH₃)₂C(CH₃)₃,—CH₂CH₂C(CH₃)₃, —CH₂CH(CH₃)CH(CH₃)₂, —CH₂CH₂C(CH₃)₂CH₂CH₃,—CH₂CH₂CH(CH₃)CH₂C(CH₃)₃, —CH₂Ph, CH₂CH₂Ph,


9. The method of claim 1, wherein the alkoxy group is —OCH₃, —OCF₃,—OCH₂CH₃, —OCH₂CH₂CH₃, —OCH₂CH₂CH₂CH₃, —OCH(CH₃)CH₂CH₃, —OCH₂CONH₂,—OCH₂CH₂N(CH₃)₂,


10. The method of claim 1, wherein the heterocyclic group is


11. The method of claim 1, wherein —COOR5 is COOCH₃, —COOCH₂CH₃,COO(CH₂)₂CH₃, —COO(CH₂)₃CH₃, COO(CH₂)₄CH₃, COOCH(CH₃)₂,


12. The method of claim 1, wherein —OCOR6 is


13. The method of claim 1, wherein —NR3R4 is —NH₂, —NHCH₃, —N(CH₃)₂,


14. The method of claim 1, wherein —NR7CYR8 is


15. The method of claim 1, wherein —NHS(O)₂R9 is


16. The method of claim 1, wherein the compound is at least one selectedfrom the group consisting of Compound 1 to Compound 155 below: Com- A =CRa, B = CRb, G = CRe, J = CRf, D = E = L = M = CH pound No. Rx Ra Rb RcRd Re Rf 1 CN H H CH₃ N(CH₃)₂ H H 2 CN H H CH₂CH₃ COOH H H 3 CN H HCH₂CH₃ N(CH₃)₂ H H 4 CN H H i-Pr Cl H H 5 CN H H i-Pr COOH H H 6 CN H Hi-Pr OCH₃ H H 7 CN H H NO₂ N(CH₃)₂ H H 8 CN H H CH₂CH₂CH₂CH₃ COOH H H 9CN H H CH(CH₃)CH₂CH₃ COOH H H 10 CN H H t-Bu COOH H H 11 CN H H t-BuOCH₃ H H 12 CN H CH₃ CH₃ OCH₃ H H 13 CN H CH₃ CH₃ COOH H H 14 CN H HCOC(CH₃)₃ OCH₃ H H 15 CN H H COC(CH₃)₃ COOH H H 16 CN H H OCH₂CH₃ OCH₃ HH 17 CN H H OCH₂CH₃ COOH H H 18 CN H H OCH₂CH₂CH₂CH₃ OCH₃ H H 19 CN H HOCH₂CH₂CH₂CH₃ COOH H H 20 CN H H CH₂Ph OCH₃ H H 21 CN H H CH₂Ph COOH H H22 CN H H NO₂ CH₂CH₃ H H 23 CN H H NO₂ i-Pro H H 24 CN H H NO₂ NH₂ H H25 CN H H NO₂

H H 26 CN H H NO₂ OCH(CH₃)CH₂CH₃ H H 27 CN H H NO₂

H H 28 CN H H NO₂ OCH₂CH₂N(CH₃)₂ H H 29 CN H H NO₂

H H 30 CN H H NO₂

H H 31 CN H H NO₂

H H 32 CN H H NO₂ H OCH₂CH₂CH(CH₃)₂ H 33 CN H H NO₂ H OCH₂CH₂CH₂N(CH₃)₂H 34 CN H H NO₂ CH₂CH(CH₃)₂ H H 35 CN H H NO₂ CH₂C(CH₃)₃ H H 36 CN H HNO₂ CH₂CH₂CH(CH₃)₂ H H 37 CN H H NO₂

H H 38 CN H H NO₂ CH₂CH₂Ph H H 39 CN H H NO₂

H H 40 CN H H NO₂

H H 41 CN H H NO₂

H H 42 CN H H NO₂ CH₂CH₂CH₂Ph H H 43 CN H H NO₂ CH₂CH₂C(CH₃)₃ H H 44 CNH H NO₂

H H 45 CN H H NO₂

H H 46 CN H H NO₂

H H 47 CN H H NO₂

H H 48 CN H H NO₂

H H 49 CN H H NO₂

H H 51 CN H H NO₂

H H 52 CN H H NO₂

H H 53 CN H H NO₂

H H 54 CN H H CH₂C(CH₃)₃ COOH H H 55 CN H H

COOH H H 56 CN H H

COOH H H 57 CN H H

COOH H H 58 CN H H

COOH H H 59 CN H H

COOH H H 60 CN H H

COOH H H 61 CN H H

COOH H H 62 CN H H

COOH H H 63 CN H H

COOH H H 64 H H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H H 65 H H H CH₂C(CH₃)₃COO(CH₂)₃CH₃ CH₃ H 66 H H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ CH₂CH₃ H 67 H CH₃ HCH₂C(CH₃)₃ COO(CH₂)₃CH₃ H H 68 H CH₂CH₃ H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H H 69H H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H CH₃ 70 H H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ CH₃CH₃ 71 H H H CH₂C(CH₃)₃ COO(CH₂)₂CH₃ H H 72 H H H CH₂C(CH₃)₃COO(CH₂)₄CH₃ H H 73 H H H CH₂C(CH₃)₃ COOCH(CH₃)₂ H H 74 H H H CH₂C(CH₃)₃

H H 75 H H H CH₂C(CH₃)₃

H H 76 H H H CH₂C(CH₃)₃ COOCH₂Ph H H 77 H H H CH₂C(CH₃)₃

H H 78 H H H CH₂CH(CH₃)CH₂CH₃ COO(CH₂)₃CH₃ H H 79 H H H

COO(CH₂)₃CH₃ H H 80 H H H

COO(CH₂)₃CH₃ H H 81 H H H

COO(CH₂)₃CH₃ H H 82 CH₃ H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H H 83 CH₃ H HCH₂C(CH₃)₃ COO(CH₂)₃CH₃ CH₃ H 84 CH₃ CH₃ H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H H85 CH₃ H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H CH₃ 86 CH₃ H H CH₂C(CH₃)₃COO(CH₂)₃CH₃ CH₃ CH₃ 87 CH₃ H H CH₂C(CH₃)₃ COO(CH₂)₂CH₃ H H 88 CH₃ H HCH₂C(CH₃)₃ COO(CH₂)₄CH₃ H H 89 CH₃ H H CH₂C(CH₃)₃ COOCH(CH₃)₂ H H 90 CH₃H H CH₂C(CH₃)₃

H H 91 CH₃ H H CH₂C(CH₃)₃

H H 92 CH₃ H H CH₂C(CH₃)₃ COOCH₂Ph H H 93 CH₃ H H CH₂C(CH₃)₃

H H 94 CH₃ H H CH₂CH(CH₃)CH₂CH₃ COO(CH₂)₃CH₃ H H 95 CH₃ H H

COO(CH₂)₃CH₃ H H 96 CH₃ H H

COO(CH₂)₃CH₃ H H 97 CH₃ H H

COO(CH₂)₃CH₃ H H 98 NH₂ H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H H 99 NH₂ H HCH₂C(CH₃)₃ COO(CH₂)₃CH₃ CH₃ H 100 NH₂ CH₃ H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H H101 NH₂ H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H CH₃ 102 NH₂ H H CH₂C(CH₃)₃COO(CH₂)₃CH₃ CH₃ CH₃ 103 NH₂ H H CH₂C(CH₃)₃ COO(CH₂)₄CH₃ H H 104 NH₂ H HCH₂C(CH₃)₃ COOCH(CH₃)₂ H H 105 NH₂ H H CH₂C(CH₃)₃

H H 106 NH₂ H H CH₂C(CH₃)₃ COOCH₂Ph H H 107 NH₂ H H CH₂C(CH₃)₃

H H 108 NH₂ H H CH₂CH(CH₃)CH₂CH₃ COO(CH₂)₃CH₃ H H 109 NH₂ H H

COO(CH₂)₃CH₃ H H 110 NH₂ H H

COO(CH₂)₃CH₃ H H 111 NH₂ H H

COO(CH2)₃CH₃ H H 112 F H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H H 113 Cl H HCH₂C(CH₃)₃ COO(CH₂)₃CH₃ CH₃ H 114 Br CH₃ H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H H115 I H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H CH₃ 116 F H H CH₂C(CH₃)₃COO(CH₂)₃CH₃ CH₃ CH₃ 117 Cl H H CH₂C(CH₃)₃ COO(CH₂)₄CH₃ H H 118 Br H HCH₂C(CH₃)₃ COOCH(CH₃)₂ H H 119 I H H CH₂C(CH₃)₃

H H 120 F H H CH₂C(CH₃)₃ COOCH₂Ph H H 121 Cl H H CH₂C(CH₃)₃

H H 122 Br H H CH₂CH(CH₃)CH₂CH₃ COO(CH₂)₃ CH₃ H 123 I H H

COO(CH₂)₃CH₃ H H 124 H H H CH₂C(CH₃)₃ COOCH₃ H H 125 H H HCH₂CH(CH₃)CH₂CH₃ COOCH₃ H H 126 H H H

COOCH₃ H H 127 H H H

COOCH₃ H H 128 H H H

COOCH₃ H H 129 H H H

COOCH₃ H H 130 H H H CH₂(CH₂)₃CH₃ COOCH₃ H H 131 H H H

COO(CH₂)₃CH₃ H H 132 H H H CH₂(CH₂)₃CH₃ COO(CH₂)₃CH₃ H H 133 H H HCH₂C(CH₃)₃

H H 134 H H H CH₂C(CH₃)₃ COOH H H 135 H H H CH₂C(CH₃)₃ COOH OH H 136 H HH CH₂C(CH₃)₃ COOH H OH 137 H H H CH₂C(CH₃)₃ COOH NH₂ H 138 H H HCH₂C(CH₃)₃ COOH H NH₂ 139 H H H CH₂C(CH₃)₃ COOH CH₃ H 140 H H HCH₂C(CH₃)₃ COOH H CH₃ 141 H H H CH₂C(CH₃)₃ CONH₂ H H 142 A = CRa, B =CRb, G = CRe, D = E = M = CH Fused ring formation R_(x) R_(a) R_(b)R_(c) R_(d) R_(e) of J and L H H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H

143 A = N, B = CRb, G = CRe, J = CRf, D = E = L = M = CH R_(x) R_(b)R_(c) R_(d) R_(e) R_(f) H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H H 144 A = CRa, B =N, G = CRe, J = CRf, D = E = L = M = CH R_(x) R_(a) R_(c) R_(d) R_(e)R_(f) H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H H 145 A = CRa, B = CRb, G = N, J =CRf, D = E = L = M = CH R_(x) R_(a) R_(b) R_(c) R_(d) R_(f) H H HCH₂C(CH₃)₃ COO(CH₂)₃CH₃ H 146 A = CRa, B = CRb, G = CRe, J = N, D = E =L = M = CH R_(x) R_(a) R_(b) R_(c) R_(d) R_(e) H H H CH₂C(CH₃)₃COO(CH₂)₃CH₃ H 147 A = CRa, B = CRb, G = CRe, J = CRf, D = E = M = CH,L= N R_(x) R_(a) R_(b) R_(c) R_(d) R_(e) R_(f) H H H CH₂C(CH₃)₃COO(CH₂)₃CH₃ H H 148 A = CRa, B = CRb, G = CRe, J = CRf, D = E = L = CH,M = N R_(x) R_(a) R_(b) R_(c) R_(d) R_(e) R_(f) H H H CH₂C(CH₃)₃COO(CH₂)₃CH₃ H H 148 A = CRa, B = CRb, G = CRe, J = CRf, M = CRg, D = E= L = CH — Rx Ra Rb Rc Rd Re Rf Rg 149 H H H CH₂C(CH₃)₃ COO(CH₂)₃CH₃ H HCOO(CH₂)₃CH₃ 150 H H H CH₂C(CH₃)₃ COOH H H OH 151 H H H CH₂C(CH₃)₃ COOHH H NH₂ 152 H H H CH₂C(CH₃)₃ COOH H H CH₃ A = CRa B = CRb, G = CRe, J =CRf, L = CRh, D = E = M = CH — Rx Ra Rb Rc Rd Re Rf Rh 153 H H HCH₂C(CH₃)₃ COOH H H OH 154 H H H CH₂C(CH₃)₃ COOH H H NH₂ 155 H H HCH₂C(CH₃)₃ COOH H H CH₃.


17. The method of claim 1, wherein the method is to prevent or treat atleast one selected from the group consisting of an infectious disease, acardiovascular disease, rheumatoid arthritis, sepsis, asthma,periodontitis, aging, alopecia, a neurodegenerative disease, and cancer.18. The method of claim 17, wherein the infectious disease comprisesHBV, HCV, HIV and influenza.